52144666
Correlation of Synaptic Inputs in the Visual Cortex of Awake, Behaving Mice
The subthreshold mechanisms that underlie neuronal correlations in awake animals are poorly understood. Here, we perform dual whole-cell recordings in the visual cortex (V1) of awake mice to investigate membrane potential (Vm) correlations between upper-layer sensory neurons. We find that the membrane potentials of neighboring neurons display large, correlated fluctuations during quiet wakefulness, including pairs of cells with disparate tuning properties. These fluctuations are driven by correlated barrages of excitation followed closely by inhibition (∼5-ms lag). During visual stimulation, low-frequency activity is diminished, and coherent high-frequency oscillations appear, even for non-preferred stimuli. These oscillations are generated by alternating excitatory and inhibitory inputs at a similar lag. The temporal sequence of depolarization for pairs of neurons is conserved during both spontaneous- and visually-evoked activity, suggesting a stereotyped flow of activation that may function to produce temporally precise "windows of opportunity" for additional synaptic inputs.
2723062
Neural correlations, population coding and computation
How the brain encodes information in population activity, and how it combines and manipulates that activity as it carries out computations, are questions that lie at the heart of systems neuroscience. During the past decade, with the advent of multi-electrode recording and improved theoretical models, these questions have begun to yield answers. However, a complete understanding of neuronal variability, and, in particular, how it affects population codes, is missing. This is because variability in the brain is typically correlated, and although the exact effects of these correlations are not known, it is known that they can be large. Here, we review studies that address the interaction between neuronal noise and population codes, and discuss their implications for population coding in general.
6831069
Measuring and interpreting neuronal correlations
Mounting evidence suggests that understanding how the brain encodes information and performs computations will require studying the correlations between neurons. The recent advent of recording techniques such as multielectrode arrays and two-photon imaging has made it easier to measure correlations, opening the door for detailed exploration of their properties and contributions to cortical processing. However, studies have reported discrepant findings, providing a confusing picture. Here we briefly review these studies and conduct simulations to explore the influence of several experimental and physiological factors on correlation measurements. Differences in response strength, the time window over which spikes are counted, spike sorting conventions and internal states can all markedly affect measured correlations and systematically bias estimates. Given these complicating factors, we offer guidelines for interpreting correlation data and a discussion of how best to evaluate the effect of correlations on cortical processing.
24452436
Decorrelated Neuronal Firing in Cortical Microcircuits
Columns, Connections, and Correlations What is the nature of interactions between neurons in neural circuits? The prevalent hypothesis suggests that dense local connectivity causes nearby cortical neurons to receive substantial amounts of common input, which in turn leads to strong correlations between them. Now two studies challenge this view, which impacts our fundamental understanding of coding in the cortex. Ecker et al. (p. 584) investigated the statistics of correlated firing in pairs of neurons from area V1 of awake macaque monkeys. In contrast to previous studies, correlations turned out to be very low, irrespective of the stimulus being shown to the animals, the distances of the recording sites, and the similarity of the neuron's receptive fields or response properties. In an accompanying modeling and recording paper, Renart et al. (p. 587) demonstrate how it is possible to have zero noise correlation, even among cells with common input. Despite dense connectivity and shared input, the firing rates of nearby neurons are largely uncorrelated. Correlated trial-to-trial variability in the activity of cortical neurons is thought to reflect the functional connectivity of the circuit. Many cortical areas are organized into functional columns, in which neurons are believed to be densely connected and to share common input. Numerous studies report a high degree of correlated variability between nearby cells. We developed chronically implanted multitetrode arrays offering unprecedented recording quality to reexamine this question in the primary visual cortex of awake macaques. We found that even nearby neurons with similar orientation tuning show virtually no correlated variability. Our findings suggest a refinement of current models of cortical microcircuit architecture and function: Either adjacent neurons share only a few percent of their inputs or, alternatively, their activity is actively decorrelated.
7348059
The mechanics of state-dependent neural correlations
Simultaneous recordings from large neural populations are becoming increasingly common. An important feature of population activity is the trial-to-trial correlated fluctuation of spike train outputs from recorded neuron pairs. Similar to the firing rate of single neurons, correlated activity can be modulated by a number of factors, from changes in arousal and attentional state to learning and task engagement. However, the physiological mechanisms that underlie these changes are not fully understood. We review recent theoretical results that identify three separate mechanisms that modulate spike train correlations: changes in input correlations, internal fluctuations and the transfer function of single neurons. We first examine these mechanisms in feedforward pathways and then show how the same approach can explain the modulation of correlations in recurrent networks. Such mechanistic constraints on the modulation of population activity will be important in statistical analyses of high-dimensional neural data.
17933714
Waking State: Rapid Variations Modulate Neural and Behavioral Responses
The state of the brain and body constantly varies on rapid and slow timescales. These variations contribute to the apparent noisiness of sensory responses at both the neural and the behavioral level. Recent investigations of rapid state changes in awake, behaving animals have provided insight into the mechanisms by which optimal sensory encoding and behavioral performance are achieved. Fluctuations in state, as indexed by pupillometry, impact both the "signal" (sensory evoked response) and the "noise" (spontaneous activity) of cortical responses. By taking these fluctuations into account, neural response (co)variability is significantly reduced, revealing the brain to be more reliable and predictable than previously thought.
14151659
Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities
Temporal and quantitative relations between excitatory and inhibitory inputs in the cortex are central to its activity, yet they remain poorly understood. In particular, a controversy exists regarding the extent of correlation between cortical excitation and inhibition. Using simultaneous intracellular recordings in pairs of nearby neurons in vivo, we found that excitatory and inhibitory inputs are continuously synchronized and correlated in strength during spontaneous and sensory-evoked activities in the rat somatosensory cortex.
23678786
Spontaneous firing patterns and axonal projections of single corticostriatal neurons in the rat medial agranular cortex.
1. Spontaneous fluctuations of membrane potential, patterns of spontaneous firing, dendritic branching patterns, and intracortical and striatal axonal arborizations were compared for two types of corticostriatal neurons in the medial agranular cortex of urethan-anesthetized rats: 1) pyramidal tract (PT) cells identified by antidromic activation from the medullary pyramid and 2) crossed corticostriatal (CST) neurons identified by antidromic activation from the contralateral neostriatum. The ipsilateral corticostriatal projections of intracellularly stained PT neurons as well as contralateral corticostriatal neurons were confirmed after labeling by intracellular injection of biocytin. 2. All well-stained PT neurons had intracortical and intrastriatal collaterals. The more common type (6 of 8) was a large, deep layer V neuron that had an extensive intracortical axon arborization but a limited axon arborization in the neostriatum. The less common type of PT neuron (2 of 8) was a medium-sized, superficial layer V neuron that had a limited intracortical axon arborization but a larger and more dense intrastriatal axonal arborization. Both subclasses of PT neurons had anatomic and physiological properties associated with slow PT cells in cats and monkeys and conduction velocities < 10 m/s. All of the PT cells but one were regular spiking cells. The exception cell fired intrinsic bursts. 3. Intracellularly stained CST neurons were located in the superficial half of layer V and the deep part of layer III. Their layer I apical dendrites were few and sparsely branched. Their axons gave rise to an extensive arbor of local axon collaterals that distributed in the region of the parent neuron, frequently extending throughout the more superficial layers, including layer I. Axon collaterals were also traced to the corpus callosum, as expected from their contralateral projections, and they contributed axon collaterals to the ipsilateral neostriatum. In the neostriatum, these axons formed extended arborizations sparsely occupying a large volume of striatal tissue. All CST neurons were regular spiking cells. 4. Both types of cells displayed spontaneous membrane fluctuations consisting of a polarized state (-60 to -90 mV) that was interrupted by 0.1- to 3.0-s periods of depolarization (-55 to -45 mV) accompanied by action potentials. The membrane potential was relatively constant in each state, and transitions between the depolarized and hyperpolarized states were sometimes periodic with a frequency of 0.3-1.5 Hz. A much faster (30-45 Hz) subthreshold oscillation of the membrane potential was observed only in the depolarized state and triggered action potentials that locked to the depolarizing peaks of this rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)
16535701
Synchronous Membrane Potential Fluctuations in Neurons of the Cat Visual Cortex
We have recorded intracellularly from pairs of neurons less than 500 microm distant from one another in V1 of anesthetized cats. Cross-correlation of spontaneous fluctuations in membrane potential revealed significant correlations between the cells in each pair. This synchronization was not dependent on the occurrence of action potentials, indicating that it was not caused by mutual interconnections. The cells were synchronized continuously rather than for brief epochs. Much weaker correlations were found between the EEG and intracellular potentials, suggesting local, rather than global, synchrony. The highest correlation occurred among cells with similar connectivity from the LGN and similar receptive fields. During visual stimulation, correlations increased when both cells responded to the stimulus and decreased when neither cell responded.
4828781
Neocortical inhibitory activities and long-range afferents contribute to the synchronous onset of silent states of the neocortical slow oscillation.
During slow-wave sleep, neurons of the thalamocortical network are engaged in a slow oscillation (<1 Hz), which consists of an alternation between the active and the silent states. Several studies have provided insights on the transition from the silent, which are essentially periods of disfacilitation, to the active states. However, the conditions leading to the synchronous onset of the silent state remain elusive. We hypothesized that a synchronous input to local inhibitory neurons could contribute to the transition to the silent state in the cat suprasylvian gyrus during natural sleep and under ketamine-xylazine anesthesia. After partial and complete deafferentation of the cortex, we found that the silent state onset was more variable among remote sites. We found that the transition to the silent state was preceded by a reduction in excitatory postsynaptic potentials and firing probability in cortical neurons. We tested the impact of chloride-mediated inhibition in the silent-state onset. We uncovered a long-duration (100-300 ms) inhibitory barrage occurring about 250 ms before the silent state onset in 3-6% of neurons during anesthesia and in 12-15% of cases during natural sleep. These inhibitory activities caused a decrease in cortical firing that reduced the excitatory drive in the neocortical network. That chain reaction of disfacilitation ends up on the silent state. Electrical stimuli could trigger a network silent state with a maximal efficacy in deep cortical layers. We conclude that long-range afferents to the neocortex and chloride-mediated inhibition play a role in the initiation of the silent state.
4822661
Global Intracellular Slow-Wave Dynamics of the Thalamocortical System
It is widely accepted that corticothalamic neurons recruit the thalamus in slow oscillation, but global slow-wave thalamocortical dynamics have never been experimentally shown. We analyzed intracellular activities of neurons either from different cortical areas or from a variety of specific and nonspecific thalamic nuclei in relation to the phase of global EEG signal in ketamine-xylazine anesthetized mice. We found that, on average, slow-wave active states started off within frontal cortical areas as well as higher-order and intralaminar thalamus (posterior and parafascicular nuclei) simultaneously. Then, the leading edge of active states propagated in the anteroposterior/lateral direction over the cortex at ∼40 mm/s. The latest structure we recorded within the slow-wave cycle was the anterior thalamus, which followed active states of the retrosplenial cortex. Active states from different cortical areas tended to terminate simultaneously. Sensory thalamic ventral posterior medial and lateral geniculate nuclei followed cortical active states with major inhibitory and weak tonic-like “modulator” EPSPs. In these nuclei, sharp-rising, large-amplitude EPSPs (“drivers”) were not modulated by cortical slow waves, suggesting their origin in ascending pathways. The thalamic active states in other investigated nuclei were composed of depolarization: some revealing “driver”- and “modulator”-like EPSPs, others showing “modulator”-like EPSPs only. We conclude that sensory thalamic nuclei follow the propagating cortical waves, whereas neurons from higher-order thalamic nuclei display “hub dynamics” and thus may contribute to the generation of cortical slow waves.
26810112
A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components
We describe a novel slow oscillation in intracellular recordings from cortical association areas 5 and 7, motor areas 4 and 6, and visual areas 17 and 18 of cats under various anesthetics. The recorded neurons (n = 254) were antidromically and orthodromically identified as corticothalamic or callosal elements receiving projections from appropriate thalamic nuclei as well as from homotopic foci in the contralateral cortex. Two major types of cells were recorded: regular- spiking (mainly slow-adapting, but also fast-adapting) neurons and intrinsically bursting cells. A group of slowly oscillating neurons (n = 21) were intracellularly stained and found to be pyramidal-shaped cells in layers III-VI, with luxuriant basal dendritic arbors. The slow rhythm appeared in 88% of recorded neurons. It consisted of slow depolarizing envelopes (lasting for 0.8–1.5 sec) with superimposed full action potentials or presumed dendritic spikes, followed by long- lasting hyperpolarizations. Such sequences recurred rhythmically at less than 1 Hz, with a prevailing oscillation between 0.3 and 0.4 Hz in 67% of urethane-anesthetized animals. While in most neurons (approximately 70%) the repetitive spikes superimposed on the slow depolarization were completely blocked by slight DC hyperpolarization, 30% of cells were found to display relatively small (3–12 mV), rapid, all-or-none potentials after obliteration of full action potentials. These fast spikes were suppressed in an all-or-none fashion at Vm more negative than -90 mV. The depolarizing envelope of the slow rhythm was reduced or suppressed at a Vm of -90 to -100 mV and its duration was greatly reduced by administration of the NMDA blocker ketamine. In keeping with this action, most (56%) neurons recorded in animals under ketamine and nitrous oxide or ketamine and xylazine anesthesia displayed the slow oscillation at higher frequencies (0.6–1 Hz) than under urethane anesthesia (0.3–0.4 Hz). In 18% of the oscillating cells, the slow rhythm mainly consisted of repetitive (15–30 Hz), relatively short-lasting (15–25 msec) IPSPs that could be revealed by bringing the Vm at more positive values than -70 mV. The long-lasting (approximately 1 sec) hyperpolarizing phase of the slow oscillation was best observed at the resting Vm and was reduced at about -100 mV. Simultaneous recording of another cell across the membrane demonstrated synchronous inhibitory periods in both neurons. Intracellular diffusion of Cl- or Cs+ reduced the amplitude and/or duration of cyclic long- lasting hyperpolaryzations.(ABSTRACT TRUNCATED AT 400 WORDS)
16232207
Spontaneous firing patterns of identified spiny neurons in the rat neostriatum
Spontaneous firing patterns of 94 unidentified neurons and 34 identified spiny neurons were compared in the neostriatum of locally anesthetized immobilized rats. Intracellular and extracellular recordings were analyzed using first order interval histograms and autocorrelograms, and neurons were identified by their somatodendritic morphology after intracellular injection of horseradish peroxidase. All neostriatal neurons tended to fire in irregular phasic bursts of activity. Considerable variation in mean firing rate, burst duration, interburst interval and the occurrence and rate of firing between bursts was apparent in both groups of neurons. There was no apparent difference between spiny neurons and the sample of unidentified extracellularly recorded neurons along any of these firing pattern parameters. Intracellular recordings from identified spiny neurons revealed noisy irregular periods of maintained 5-20 mV membrane depolarizations which corresponded to the occurrence of bursts of firing in spontaneously active neurons. These depolarizations occurred in neostriatal neurons exhibiting no spontaneous activity but were of insufficient amplitude to trigger impulse activity.
1407218
Membrane Potential Synchrony in Primary Visual Cortex during Sensory Stimulation
When the primary visual cortex (V1) is activated by sensory stimulation, what is the temporal correlation between the synaptic inputs to nearby neurons? This question underlies the origin of correlated activity, the mechanism of how visually evoked activity emerges and propagates in cortical circuits, and the relationship between spontaneous and evoked activity. Here, we have recorded membrane potential from pairs of V1 neurons in anesthetized cats and found that visual stimulation suppressed low-frequency membrane potential synchrony (0-10 Hz), and often increased synchrony at high frequencies (20-80 Hz). The increase in high-frequency synchrony occurred for neurons with similar orientation preferences and for neurons with different orientation preferences and occurred for a wide range of stimulus orientations. Thus, while only a subset of neurons spike in response to visual stimulation, a far larger proportion of the circuit is correlated with spiking activity through subthreshold, high-frequency synchronous activity that crosses functional domains.
26314243
Correlating whisker behavior with membrane potential in barrel cortex of awake mice
To investigate synaptic events underlying sensory perception, we made whole-cell membrane potential recordings of barrel cortex neurons in awake mice while recording whisker-related behavior. During quiet periods, we recorded slow, large-amplitude membrane potential changes, which switched during whisking to small, fast fluctuations that were correlated with whisker position. Robust subthreshold responses were evoked by passive whisker stimulation during quiet behavior and by active whisker contact with an object.
8445122
Subthreshold Mechanisms Underlying State-Dependent Modulation of Visual Responses
The processing of sensory information varies widely across behavioral states. However, little is known about how behavioral states modulate the intracellular activity of cortical neurons to effect changes in sensory responses. Here, we performed whole-cell recordings from neurons in upper-layer primary visual cortex of awake mice during locomotion and quiet wakefulness. We found that the signal-to-noise ratio for sensory responses was improved during locomotion by two mechanisms: (1) a decrease in membrane potential variability leading to a reduction in background firing rates and (2) an enhancement in the amplitude and reliability of visually evoked subthreshold responses mediated by an increase in total conductance and a depolarization of the stimulus-evoked reversal potential. Consistent with the enhanced signal-to-noise ratio for visual responses during locomotion, we demonstrate that performance is improved in a visual detection task during this behavioral state.
23018655
Visually Evoked 3–5 Hz Membrane Potential Oscillations Reduce the Responsiveness of Visual Cortex Neurons in Awake Behaving Mice
Low-frequency membrane potential (Vm) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low-frequency Vm oscillations have been described in inactive awake animals, but it is unclear whether they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell Vm recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks. We recorded stereotyped 3–5 Hz Vm oscillations where the Vm baseline hyperpolarized as the Vm underwent high amplitude rhythmic fluctuations lasting 1–2 s in duration. When 3–5 Hz Vm oscillations coincided with visual cues, excitatory neuron responses to preferred cues were significantly reduced. Despite this disruption to sensory processing, visual cues were critical for evoking 3–5 Hz Vm oscillations when animals performed discrimination tasks and passively viewed drifting grating stimuli. Using pupillometry and animal locomotive speed as indicators of arousal, we found that 3–5 Hz oscillations were not restricted to unaroused states and that they occurred equally in aroused and unaroused states. Therefore, low-frequency Vm oscillations play a role in shaping sensory processing in visual cortical neurons, even during active wakefulness and decision making. SIGNIFICANCE STATEMENT A neuron's membrane potential (Vm) strongly shapes how information is processed in sensory cortices of awake animals. Yet, very little is known about how low-frequency Vm oscillations influence sensory processing and whether they occur in aroused awake animals. By performing two-photon guided whole-cell recordings from layer 2/3 excitatory and inhibitory neurons in the visual cortex of awake behaving animals, we found visually evoked stereotyped 3–5 Hz Vm oscillations that disrupt excitatory responsiveness to visual stimuli. Moreover, these oscillations occurred when animals were in high and low arousal states as measured by animal speed and pupillometry. These findings show, for the first time, that low-frequency Vm oscillations can significantly modulate sensory signal processing, even in awake active animals.
1585956
Cortical Membrane Potential Signature of Optimal States for Sensory Signal Detection
The neural correlates of optimal states for signal detection task performance are largely unknown. One hypothesis holds that optimal states exhibit tonically depolarized cortical neurons with enhanced spiking activity, such as occur during movement. We recorded membrane potentials of auditory cortical neurons in mice trained on a challenging tone-in-noise detection task while assessing arousal with simultaneous pupillometry and hippocampal recordings. Arousal measures accurately predicted multiple modes of membrane potential activity, including rhythmic slow oscillations at low arousal, stable hyperpolarization at intermediate arousal, and depolarization during phasic or tonic periods of hyper-arousal. Walking always occurred during hyper-arousal. Optimal signal detection behavior and sound-evoked responses, at both sub-threshold and spiking levels, occurred at intermediate arousal when pre-decision membrane potentials were stably hyperpolarized. These results reveal a cortical physiological signature of the classically observed inverted-U relationship between task performance and arousal and that optimal detection exhibits enhanced sensory-evoked responses and reduced background synaptic activity.
17527528
Cellular mechanisms of brain-state-dependent gain modulation in visual cortex
Visual cortical neurons fire at higher rates to visual stimuli during locomotion than during immobility, while maintaining orientation selectivity. The mechanisms underlying this change in gain are not understood. We performed whole-cell recordings from layer 2/3 and layer 4 visual cortical excitatory neurons and from parvalbumin-positive and somatostatin-positive inhibitory neurons in mice that were free to rest or run on a spherical treadmill. We found that the membrane potential of all cell types became more depolarized and (with the exception of somatostatin-positive interneurons) less variable during locomotion. Cholinergic input was essential for maintaining the unimodal membrane potential distribution during immobility, whereas noradrenergic input was necessary for the tonic depolarization associated with locomotion. Our results provide a mechanism for how neuromodulation controls the gain and signal-to-noise ratio of visual cortical neurons during changes in the state of vigilance.
14118354
Pupil Fluctuations Track Fast Switching of Cortical States during Quiet Wakefulness
Neural responses are modulated by brain state, which varies with arousal, attention, and behavior. In mice, running and whisking desynchronize the cortex and enhance sensory responses, but the quiescent periods between bouts of exploratory behaviors have not been well studied. We found that these periods of "quiet wakefulness" were characterized by state fluctuations on a timescale of 1-2 s. Small fluctuations in pupil diameter tracked these state transitions in multiple cortical areas. During dilation, the intracellular membrane potential was desynchronized, sensory responses were enhanced, and population activity was less correlated. In contrast, constriction was characterized by increased low-frequency oscillations and higher ensemble correlations. Specific subtypes of cortical interneurons were differentially activated during dilation and constriction, consistent with their participation in the observed state changes. Pupillometry has been used to index attention and mental effort in humans, but the intracellular dynamics and differences in population activity underlying this phenomenon were previously unknown.
4458670
A synaptic and circuit basis for corollary discharge in the auditory cortex
Sensory regions of the brain integrate environmental cues with copies of motor-related signals important for imminent and ongoing movements. In mammals, signals propagating from the motor cortex to the auditory cortex are thought to have a critical role in normal hearing and behaviour, yet the synaptic and circuit mechanisms by which these motor-related signals influence auditory cortical activity remain poorly understood. Using in vivo intracellular recordings in behaving mice, we find that excitatory neurons in the auditory cortex are suppressed before and during movement, owing in part to increased activity of local parvalbumin-positive interneurons. Electrophysiology and optogenetic gain- and loss-of-function experiments reveal that motor-related changes in auditory cortical dynamics are driven by a subset of neurons in the secondary motor cortex that innervate the auditory cortex and are active during movement. These findings provide a synaptic and circuit basis for the motor-related corollary discharge hypothesized to facilitate hearing and auditory-guided behaviours.
8255425
Membrane Potential Dynamics of GABAergic Neurons in the Barrel Cortex of Behaving Mice
Computations in cortical circuits are mediated by synaptic interactions between excitatory and inhibitory neurons, and yet we know little about their activity in awake animals. Here, through single and dual whole-cell recordings combined with two-photon microscopy in the barrel cortex of behaving mice, we directly compare the synaptically driven membrane potential dynamics of inhibitory and excitatory layer 2/3 neurons. We find that inhibitory neurons depolarize synchronously with excitatory neurons, but they are much more active with differential contributions of two classes of inhibitory neurons during different brain states. Fast-spiking GABAergic neurons dominate during quiet wakefulness, but during active wakefulness Non-fast-spiking GABAergic neurons depolarize, firing action potentials at increased rates. Sparse uncorrelated action potential firing in excitatory neurons is driven by fast, large, and cell-specific depolarization. In contrast, inhibitory neurons fire correlated action potentials at much higher frequencies driven by slower, smaller, and broadly synchronized depolarization.
594875
Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex
Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex of awake behaving mice. SOM neurons were spontaneously active during periods of quiet wakefulness. However, SOM neurons hyperpolarized and reduced action potential firing in response to both passive and active whisker sensing, in contrast with all other recorded types of nearby neurons, which were excited by sensory input. Optogenetic inhibition of SOM neurons increased burst firing in nearby excitatory neurons. We hypothesize that the spontaneous activity of SOM neurons during quiet wakefulness provides a tonic inhibition to the distal dendrites of excitatory pyramidal neurons. Conversely, the inhibition of SOM cells during active cortical processing likely enhances distal dendritic excitability, which may be important for top-down computations and sensorimotor integration.
982790
Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice
Internal brain states form key determinants for sensory perception, sensorimotor coordination and learning. A prominent reflection of different brain states in the mammalian central nervous system is the presence of distinct patterns of cortical synchrony, as revealed by extracellular recordings of the electroencephalogram, local field potential and action potentials. Such temporal correlations of cortical activity are thought to be fundamental mechanisms of neuronal computation. However, it is unknown how cortical synchrony is reflected in the intracellular membrane potential (Vm) dynamics of behaving animals. Here we show, using dual whole-cell recordings from layer 2/3 primary somatosensory barrel cortex in behaving mice, that the Vm of nearby neurons is highly correlated during quiet wakefulness. However, when the mouse is whisking, an internally generated state change reduces the Vm correlation, resulting in a desynchronized local field potential and electroencephalogram. Action potential activity was sparse during both quiet wakefulness and active whisking. Single action potentials were driven by a large, brief and specific excitatory input that was not present in the Vm of neighbouring cells. Action potential initiation occurs with a higher signal-to-noise ratio during active whisking than during quiet periods. Therefore, we show that an internal brain state dynamically regulates cortical membrane potential synchrony during behaviour and defines different modes of cortical processing.
19004279
Translaminar Cortical Membrane Potential Synchrony in Behaving Mice
Summary The synchronized activity of six layers of cortical neurons is critical for sensory perception and the control of voluntary behavior, but little is known about the synaptic mechanisms of cortical synchrony across layers in behaving animals. We made single and dual whole-cell recordings from the primary somatosensory forepaw cortex in awake mice and show that L2/3 and L5 excitatory neurons have layer-specific intrinsic properties and membrane potential dynamics that shape laminar-specific firing rates and subthreshold synchrony. First, while sensory and movement-evoked synaptic input was tightly correlated across layers, spontaneous action potentials and slow spontaneous subthreshold fluctuations had laminar-specific timing; second, longer duration forepaw movement was associated with a decorrelation of subthreshold activity; third, spontaneous and sensory-evoked forepaw movements were signaled more strongly by L5 than L2/3 neurons. Together, our data suggest that the degree of translaminar synchrony is dependent upon the origin (sensory, spontaneous, and movement) of the synaptic input.
205231607
Inhibition dominates sensory responses in awake cortex
The activity of the cerebral cortex is thought to depend on the precise relationship between synaptic excitation and inhibition. In the visual cortex, in particular, intracellular measurements have related response selectivity to coordinated increases in excitation and inhibition. These measurements, however, have all been made during anaesthesia, which strongly influences cortical state and therefore sensory processing. The synaptic activity that is evoked by visual stimulation during wakefulness is unknown. Here we measured visually evoked responses—and the underlying synaptic conductances—in the visual cortex of anaesthetized and awake mice. Under anaesthesia, responses could be elicited from a large region of visual space and were prolonged. During wakefulness, responses were more spatially selective and much briefer. Whole-cell patch-clamp recordings of synaptic conductances showed a difference in synaptic inhibition between the two conditions. Under anaesthesia, inhibition tracked excitation in amplitude and spatial selectivity. By contrast, during wakefulness, inhibition was much stronger than excitation and had extremely broad spatial selectivity. We conclude that during wakefulness, cortical responses to visual stimulation are dominated by synaptic inhibition, restricting the spatial spread and temporal persistence of neural activity. These results provide a direct glimpse of synaptic mechanisms that control sensory responses in the awake cortex.
4409655
Sensory stimulation shifts visual cortex from synchronous to asynchronous states
In the mammalian cerebral cortex, neural responses are highly variable during spontaneous activity and sensory stimulation. To explain this variability, the cortex of alert animals has been proposed to be in an asynchronous high-conductance state in which irregular spiking arises from the convergence of large numbers of uncorrelated excitatory and inhibitory inputs onto individual neurons. Signatures of this state are that a neuron’s membrane potential (Vm) hovers just below spike threshold, and its aggregate synaptic input is nearly Gaussian, arising from many uncorrelated inputs. Alternatively, irregular spiking could arise from infrequent correlated input events that elicit large fluctuations in Vm (refs 5, 6). To distinguish between these hypotheses, we developed a technique to perform whole-cell Vm measurements from the cortex of behaving monkeys, focusing on primary visual cortex (V1) of monkeys performing a visual fixation task. Here we show that, contrary to the predictions of an asynchronous state, mean Vm during fixation was far from threshold (14 mV) and spiking was triggered by occasional large spontaneous fluctuations. Distributions of Vm values were skewed beyond that expected for a range of Gaussian input, but were consistent with synaptic input arising from infrequent correlated events. Furthermore, spontaneous fluctuations in Vm were correlated with the surrounding network activity, as reflected in simultaneously recorded nearby local field potential. Visual stimulation, however, led to responses more consistent with an asynchronous state: mean Vm approached threshold, fluctuations became more Gaussian, and correlations between single neurons and the surrounding network were disrupted. These observations show that sensory drive can shift a common cortical circuitry from a synchronous to an asynchronous state.
9979112
Millisecond Coupling of Local Field Potentials to Synaptic Currents in the Awake Visual Cortex
Summary The cortical local field potential (LFP) is a common measure of population activity, but its relationship to synaptic activity in individual neurons is not fully established. This relationship has been typically studied during anesthesia and is obscured by shared slow fluctuations. Here, we used patch-clamp recordings in visual cortex of anesthetized and awake mice to measure intracellular activity; we then applied a simple method to reveal its coupling to the simultaneously recorded LFP. LFP predicted membrane potential as accurately as synaptic currents, indicating a major role for synaptic currents in the relationship between cortical LFP and intracellular activity. During anesthesia, cortical LFP predicted excitation far better than inhibition; during wakefulness, it predicted them equally well, and visual stimulation further enhanced predictions of inhibition. These findings reveal a central role for synaptic currents, and especially inhibition, in the relationship between the subthreshold activity of individual neurons and the cortical LFP during wakefulness.
9742937
Local Origin of Field Potentials in Visual Cortex
The local field potential (LFP) is increasingly used to measure the combined activity of neurons within a region of tissue. Yet, available estimates of the size of this region are highly disparate, ranging from several hundred microns to a few millimeters. To measure the size of this region directly, we used a combination of multielectrode recordings and optical imaging. We determined the orientation selectivity of stimulus-evoked LFP signals in primary visual cortex and were able to predict it on the basis of the surrounding map of orientation preference. The results show that > 95% of the LFP signal originates within 250 microm of the recording electrode. This quantitative estimate indicates that LFPs are more local than often recognized and provides a guide to the interpretation of the increasing number of studies that rest on LFP recordings.
10713897
Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice
We report a technique for two-photon fluorescence imaging with cellular resolution in awake, behaving mice with minimal motion artifact. The apparatus combines an upright, table-mounted two-photon microscope with a spherical treadmill consisting of a large, air-supported Styrofoam ball. Mice, with implanted cranial windows, are head restrained under the objective while their limbs rest on the ball's upper surface. Following adaptation to head restraint, mice maneuver on the spherical treadmill as their heads remain motionless. Image sequences demonstrate that running-associated brain motion is limited to approximately 2-5 microm. In addition, motion is predominantly in the focal plane, with little out-of-plane motion, making the application of a custom-designed Hidden-Markov-Model-based motion correction algorithm useful for postprocessing. Behaviorally correlated calcium transients from large neuronal and astrocytic populations were routinely measured, with an estimated motion-induced false positive error rate of <5%.
9093301
The Subthreshold Relation between Cortical Local Field Potential and Neuronal Firing Unveiled by Intracellular Recordings in Awake Rats
In most of the in vivo electrophysiological studies of cortical processing, which are extracellular, the spike-triggered local field potential average (LFP STA) is the measure used to estimate the correlation between the synaptic inputs of individual neuron and the local population. To understand how the magnitude and shape of LFP STA reflect the underlying correlation of synaptic activities, the membrane potential of the firing neuron has to be recorded together with the LFP. Using intracellular recordings from the cortex of awake rats, we found that for a large range of firing rates and for different behavioral states, the LFP STA represents both in its waveform and its magnitude the cross-correlation between the membrane potential of the neuron and the LFP. This data, supported by further analysis, suggests that LFP STA does not represent large network events specific to the spike times, but rather the synchrony between the mean synaptic activity of the population and the membrane potential of the single neuron, present both around spike times and in the intervals between spikes. Furthermore, it introduces a novel interpretation of the available data from unit and LFP extracellular recording experiments.
10480680
Area map of mouse visual cortex
It is controversial whether mouse extrastriate cortex has a “simple” organization in which lateral primary visual cortex (V1) is adjoined by a single area V2 or has a “complex” organization, in which lateral V1 is adjoined by multiple distinct areas, all of which share the vertical meridian with V1. Resolving this issue is important for understanding the evolution and development of cortical arealization. We have used triple pathway tracing combined with receptive field recordings to map azimuth and elevation in the same brain and have referenced these maps against callosal landmarks. We found that V1 projects to 15 cortical fields. At least nine of these contain maps with complete and orderly representations of the entire visual hemifield and therefore represent distinct areas. One of these, PM, adjoins V1 at the medial border. Five areas, P, LM, AL, RL, and A, adjoin V1 on the lateral border, but only LM shares the vertical meridian representation with V1. This suggests that LM is homologous to V2 and that the lateral extrastriate areas do not represent modules within a single area V2. Thus, mouse visual cortex is “simple” in the sense that lateral V1 is adjoined by a single V2‐like area, LM, and “complex” in having a string of areas in lateral extrastriate cortex, which receive direct V1 input. The results suggest that large numbers of areas with topologically equivalent maps of the visual field emerge early in evolution and that homologous areas are inherited in different mammalian lineages. J. Comp. Neurol. 502:339–357, 2007. © 2007 Wiley‐Liss, Inc.
4383888
The emergence of functional microcircuits in visual cortex
Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured and excitatory neurons form subnetworks that process related sensory information. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience—a process that may be facilitated by early electrical coupling between neuronal subsets—and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.
1326580
Modulation of Visual Responses by Behavioral State in Mouse Visual Cortex
Studies of visual processing in rodents have conventionally been performed on anesthetized animals, precluding examination of the effects of behavior on visually evoked responses. We have now studied the response properties of neurons in primary visual cortex of awake mice that were allowed to run on a freely rotating spherical treadmill with their heads fixed. Most neurons showed more than a doubling of visually evoked firing rate as the animal transitioned from standing still to running, without changes in spontaneous firing or stimulus selectivity. Tuning properties in the awake animal were similar to those measured previously in anesthetized animals. Response magnitude in the lateral geniculate nucleus did not increase with locomotion, demonstrating that the striking change in responsiveness did not result from peripheral effects at the eye. Interestingly, some narrow-spiking cells were spontaneously active during running but suppressed by visual stimuli. These results demonstrate powerful cell-type-specific modulation of visual processing by behavioral state in awake mice.
1546069
Functional specificity of local synaptic connections in neocortical networks
Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.
2218896
Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: an intracellular study.
Earlier extracellular recordings during natural sleep have shown that, during slow-wave sleep (SWS), neocortical neurons display long-lasting periods of silence, whereas they are tonically active and discharge at higher rates during waking and sleep with rapid eye movements (REMs). We analyzed the nature of long-lasting periods of neuronal silence in SWS and the changes in firing rates related to ocular movements during REM sleep and waking using intracellular recordings from electrophysiologically identified neocortical neurons in nonanesthetized and nonparalyzed cats. We found that the silent periods during SWS are associated with neuronal hyperpolarizations, which are due to a mixture of K(+) currents and disfacilitation processes. Conventional fast-spiking neurons (presumably local inhibitory interneurons) increased their firing rates during REMs and eye movements in waking. During REMs, the firing rates of regular-spiking neurons from associative areas decreased and intracellular traces revealed numerous, short-lasting, low-amplitude inhibitory postsynaptic potentials (IPSPs), that were reversed after intracellular chloride infusion. In awake cats, regular-spiking neurons could either increase or decrease their firing rates during eye movements. The short-lasting IPSPs associated with eye movements were still present in waking; they preceded the spikes and affected their timing. We propose that there are two different forms of firing rate control: disfacilitation induces long-lasting periods of silence that occur spontaneously during SWS, whereas active inhibition, consisting of low-amplitude, short-lasting IPSPs, is prevalent during REMs and precisely controls the timing of action potentials in waking.
4110737
A cortical–hippocampal–cortical loop of information processing during memory consolidation
Hippocampal replay during sharp-wave ripple events (SWRs) is thought to drive memory consolidation in hippocampal and cortical circuits. Changes in neocortical activity can precede SWR events, but whether and how these changes influence the content of replay remains unknown. Here we show that during sleep there is a rapid cortical–hippocampal–cortical loop of information flow around the times of SWRs. We recorded neural activity in auditory cortex (AC) and hippocampus of rats as they learned a sound-guided task and during sleep. We found that patterned activation in AC precedes and predicts the subsequent content of hippocampal activity during SWRs, while hippocampal patterns during SWRs predict subsequent AC activity. Delivering sounds during sleep biased AC activity patterns, and sound-biased AC patterns predicted subsequent hippocampal activity. These findings suggest that activation of specific cortical representations during sleep influences the identity of the memories that are consolidated into long-term stores.
1956539
Coordinated Interactions between Hippocampal Ripples and Cortical Spindles during Slow-Wave Sleep
Sleep is characterized by a structured combination of neuronal oscillations. In the hippocampus, slow-wave sleep (SWS) is marked by high-frequency network oscillations (approximately 200 Hz "ripples"), whereas neocortical SWS activity is organized into low-frequency delta (1-4 Hz) and spindle (7-14 Hz) oscillations. While these types of hippocampal and cortical oscillations have been studied extensively in isolation, the relationships between them remain unknown. Here, we demonstrate the existence of temporal correlations between hippocampal ripples and cortical spindles that are also reflected in the correlated activity of single neurons within these brain structures. Spindle-ripple episodes may thus constitute an important mechanism of cortico-hippocampal communication during sleep. This coactivation of hippocampal and neocortical pathways may be important for the process of memory consolidation, during which memories are gradually translated from short-term hippocampal to longer-term neocortical stores.
18609467
Communication between neocortex and hippocampus during sleep in rodents
Both neocortical and hippocampal networks organize the firing patterns of their neurons by prominent oscillations during sleep, but the functional role of these rhythms is not well understood. Here, we show a robust correlation of neuronal discharges between the somatosensory cortex and hippocampus on both slow and fine time scales in the mouse and rat. Neuronal bursts in deep cortical layers, associated with sleep spindles and delta waves/slow rhythm, effectively triggered hippocampal discharges related to fast (ripple) oscillations. We hypothesize that oscillation-mediated temporal links coordinate specific information transfer between neocortical and hippocampal cell assemblies. Such a neocortical–hippocampal interplay may be important for memory consolidation.
498489
Fast-Forward Playback of Recent Memory Sequences in Prefrontal Cortex During Sleep
As previously shown in the hippocampus and other brain areas, patterns of firing-rate correlations between neurons in the rat medial prefrontal cortex during a repetitive sequence task were preserved during subsequent sleep, suggesting that waking patterns are reactivated. We found that, during sleep, reactivation of spatiotemporal patterns was coherent across the network and compressed in time by a factor of 6 to 7. Thus, when behavioral constraints are removed, the brain's intrinsic processing speed may be much faster than it is in real time. Given recent evidence implicating the medial prefrontal cortex in retrieval of long-term memories, the observed replay may play a role in the process of memory consolidation.
3005845
Choice-specific sequences in parietal cortex during a virtual-navigation decision task
The posterior parietal cortex (PPC) has an important role in many cognitive behaviours; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioural choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (<100 micrometres). During working memory decision tasks, the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits.
11767344
Relationship between spontaneous and evoked spike-time correlations in primate visual cortex.
Coincident spikes have been implicated in vision-related processes such as feature binding, gain modulation, and long-distance communication. The source of these spike-time correlations is unknown. Although several studies have proposed that cortical spikes are correlated based on stimulus structure, others have suggested that spike-time correlations reflect ongoing cortical activity present even in the absence of a coherent visual stimulus. To examine this issue, we collected single-unit recordings from primary visual cortex (V1) of the anesthetized and paralyzed prosimian bush baby using a 100-electrode array. Spike-time correlations for pairs of cells were compared under three conditions: a moving grating at the cells' preferred orientation, an equiluminant blank screen, and a dark condition with eyes covered. The amplitudes, lags, and widths of cross-correlation histograms (CCHs) were strongly correlated between these conditions although for the blank stimulus and dark condition, the CCHs were broader with peaks lower in amplitude. In both preferred stimulus and blank conditions, the CCH amplitudes were greater when the cells within the pair had overlapping receptive fields and preferred similar orientations rather than nonoverlapping receptive fields and different orientations. These data suggest that spike-time correlations present in evoked activity are generated by mechanisms common to those operating in spontaneous conditions.
205431067
Coordinated memory replay in the visual cortex and hippocampus during sleep
Sleep replay of awake experience in the cortex and hippocampus has been proposed to be involved in memory consolidation. However, whether temporally structured replay occurs in the cortex and whether the replay events in the two areas are related are unknown. Here we studied multicell spiking patterns in both the visual cortex and hippocampus during slow-wave sleep in rats. We found that spiking patterns not only in the cortex but also in the hippocampus were organized into frames, defined as periods of stepwise increase in neuronal population activity. The multicell firing sequences evoked by awake experience were replayed during these frames in both regions. Furthermore, replay events in the sensory cortex and hippocampus were coordinated to reflect the same experience. These results imply simultaneous reactivation of coherent memory traces in the cortex and hippocampus during sleep that may contribute to or reflect the result of the memory consolidation process.
59742572
Corticonics: Neural Circuits of Cerebral Cortex
Preface 1. Anatomy of the cerebral cortex 2. The probability for synaptic contact between neurons in the cortex 3. Processing of spikes by neural networks 4. Relations between membrane potential and the synaptic response curve 5. Models of neural networks 6. Transmission through chains of neurons 7. Synchronous transmission Appendix Index.
24970588
Synaptic Mechanisms of Tight Spike Synchrony at Gamma Frequency in Cerebral Cortex
During the generation of higher-frequency (e.g., gamma) oscillations, cortical neurons can exhibit pairwise tight (<10 ms) spike synchrony. To understand how synaptic currents contribute to rhythmic activity and spike synchrony, we performed dual whole-cell recordings in mouse entorhinal cortical slices generating periodic activity (the slow oscillation). This preparation exhibited a significant amount of gamma-coherent spike synchrony during the active phase of the slow oscillation (Up state), particularly among fast-spiking inhibitory interneurons. IPSCs arriving in pairs of either pyramidal or fast-spiking neurons during the Up state were highly synchronized and exhibited significant coherence at frequencies from 10 to 100 Hz, peaking at ∼40 Hz, suggesting both synchronous discharge of, and synaptic divergence from, nearby inhibitory neurons. By inferring synaptic currents related to spike generation in simultaneously recorded pyramidal or fast-spiking neurons, we detected a decay of inhibition ∼20 ms before spiking. In fast-spiking interneurons, this was followed by an even larger excitatory input immediately before spike generation. Consistent with an important role for phasic excitation in driving spiking, we found that the correlation of excitatory inputs was highly predictive of spike synchrony in pairs of fast-spiking interneurons. Interestingly, spike synchrony in fast-spiking interneurons was not related to the strength of gap junctional coupling, and was still prevalent in connexin 36 knock-out animals. Our results support the pyramidal-interneuron gamma model of fast rhythmic oscillation in the cerebral cortex and suggest that spike synchrony and phase preference arises from the precise interaction of excitatory–inhibitory postsynaptic currents. SIGNIFICANCE STATEMENT We dissected the cellular and synaptic basis of spike synchrony occurring at gamma frequency (30–80 Hz). We used simultaneous targeted whole-cell recordings in an active slice preparation and analyzed the relationships between synaptic inputs and spike generation. We found that both pyramidal and fast-spiking neurons receive large, coherent inhibitory synaptic inputs at gamma frequency. In addition, we found that fast-spiking interneurons receive large, phasic excitatory synaptic inputs immediately before spike generation followed shortly by synaptic inhibition. These data support the principal-interneuron gamma generation model, and reveal how the synaptic connectivity between excitatory and inhibitory neurons supports the generation of gamma oscillations and spike synchrony.
839664
Mechanisms of gamma oscillations.
Gamma rhythms are commonly observed in many brain regions during both waking and sleep states, yet their functions and mechanisms remain a matter of debate. Here we review the cellular and synaptic mechanisms underlying gamma oscillations and outline empirical questions and controversial conceptual issues. Our main points are as follows: First, gamma-band rhythmogenesis is inextricably tied to perisomatic inhibition. Second, gamma oscillations are short-lived and typically emerge from the coordinated interaction of excitation and inhibition, which can be detected as local field potentials. Third, gamma rhythm typically concurs with irregular firing of single neurons, and the network frequency of gamma oscillations varies extensively depending on the underlying mechanism. To document gamma oscillations, efforts should be made to distinguish them from mere increases of gamma-band power and/or increased spiking activity. Fourth, the magnitude of gamma oscillation is modulated by slower rhythms. Such cross-frequency coupling may serve to couple active patches of cortical circuits. Because of their ubiquitous nature and strong correlation with the "operational modes" of local circuits, gamma oscillations continue to provide important clues about neuronal population dynamics in health and disease.
4846947
Origin of slow cortical oscillations in deafferented cortical slabs.
An in vivo preparation has been developed to study the mechanisms underlying spontaneous sleep oscillations. Dual and triple simultaneous intracellular recordings were made from neurons in small isolated cortical slabs (10 mm x 6 mm) in anesthetized cats. Spontaneously occurring slow sleep oscillations, present in the adjacent intact cortex, were absent in small slabs. However, the isolated slabs displayed brief active periods separated by long periods of silence, up to 60 s in duration. During these silent periods, 60% of neurons showed non-linear amplification of low-amplitude depolarizing activity. Nearly 40% of the cells, twice as many as in intact cortex, were classified as intrinsically bursting. In cortical network models based on Hodgkin-Huxley-like neurons, the summation of simulated spontaneous miniature excitatory postsynaptic potentials was sufficient to activate a persistent sodium current, initiating action potentials in single neurons that then spread through the network. Consistent with this model, enlarging the isolated cortical territory to an isolated gyrus (30 mm x 20 mm) increased the probability of initiating large-scale activity. In these larger territories, both the frequency and regularity of the slow oscillation approached that generated in intact cortex. The frequency of active periods in an analytical model of the cortical network accurately predicted the scaling observed in simulations and from recordings in cortical slabs of increasing size.
7563756
Layer-specific excitatory circuits differentially control recurrent network dynamics in the neocortex
In the absence of external stimuli, the mammalian neocortex shows intrinsic network oscillations. These dynamics are characterized by translaminar assemblies of neurons whose activity synchronizes rhythmically in space and time. How different cortical layers influence the formation of these spontaneous cellular assemblies is poorly understood. We found that excitatory neurons in supragranular and infragranular layers have distinct roles in the regulation of intrinsic low-frequency oscillations in mice in vivo. Optogenetic activation of infragranular neurons generated network activity that resembled spontaneous events, whereas photoinhibition of these same neurons substantially attenuated slow ongoing dynamics. In contrast, light activation and inhibition of supragranular cells had modest effects on spontaneous slow activity. This study represents, to the best of our knowledge, the first causal demonstration that excitatory circuits located in distinct cortical layers differentially control spontaneous low-frequency dynamics.
4387337
A neural circuit for spatial summation in visual cortex
The response of cortical neurons to a sensory stimulus is modulated by the context. In the visual cortex, for example, stimulation of a pyramidal cell's receptive-field surround can attenuate the cell’s response to a stimulus in the centre of its receptive field, a phenomenon called surround suppression. Whether cortical circuits contribute to surround suppression or whether the phenomenon is entirely relayed from earlier stages of visual processing is debated. Here we show that, in contrast to pyramidal cells, the response of somatostatin-expressing inhibitory neurons (SOMs) in the superficial layers of the mouse visual cortex increases with stimulation of the receptive-field surround. This difference results from the preferential excitation of SOMs by horizontal cortical axons. By perturbing the activity of SOMs, we show that these neurons contribute to pyramidal cells' surround suppression. These results establish a cortical circuit for surround suppression and attribute a particular function to a genetically defined type of inhibitory neuron.
17881742
Motor Cortex Feedback Influences Sensory Processing by Modulating Network State
Long-range corticocortical communication may have important roles in context-dependent sensory processing, yet we know very little about how these pathways influence their target regions. We studied the influence of primary motor cortex activity on primary somatosensory cortex in the mouse whisker system. We show that primary motor and somatosensory cortices undergo coherent, context-dependent changes in network state. Moreover, we show that motor cortex activity can drive changes in somatosensory cortex network state. A series of experiments demonstrate the involvement of the direct corticocortical feedback pathway, providing temporally precise and spatially targeted modulation of network dynamics. Cortically mediated changes in network state significantly impact sensory coding, with activated states increasing the reliability of responses to complex stimuli. By influencing network state, corticocortical communication from motor cortex may ensure that during active exploration the relevant sensory region is primed for enhanced sensory discrimination.
15216287
Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex
Rapid variations in cortical state during wakefulness have a strong influence on neural and behavioural responses and are tightly coupled to changes in pupil size across species. However, the physiological processes linking cortical state and pupil variations are largely unknown. Here we demonstrate that these rapid variations, during both quiet waking and locomotion, are highly correlated with fluctuations in the activity of corticopetal noradrenergic and cholinergic projections. Rapid dilations of the pupil are tightly associated with phasic activity in noradrenergic axons, whereas longer-lasting dilations of the pupil, such as during locomotion, are accompanied by sustained activity in cholinergic axons. Thus, the pupil can be used to sensitively track the activity in multiple neuromodulatory transmitter systems as they control the state of the waking brain.
9731538
Basal Forebrain Activation Enhances Cortical Coding of Natural Scenes
The nucleus basalis of the basal forebrain is an essential component of the neuromodulatory system controlling the behavioral state of an animal and it is thought to be important in regulating arousal and attention. However, the effect of nucleus basalis activation on sensory processing remains poorly understood. Using polytrode recording in rat visual cortex, we found that nucleus basalis stimulation caused prominent decorrelation between neurons and marked improvement in the reliability of neuronal responses to natural scenes. The decorrelation depended on local activation of cortical muscarinic acetylcholine receptors, whereas the increased reliability involved distributed neural circuits, as evidenced by nucleus basalis–induced changes in thalamic responses. Further analysis showed that the decorrelation and increased reliability improved cortical representation of natural stimuli in a complementary manner. Thus, the basal forebrain neuromodulatory circuit, which is known to be activated during aroused and attentive states, acts through both local and distributed mechanisms to improve sensory coding.
17323916
Effects and Mechanisms of Wakefulness on Local Cortical Networks
Mammalian brains generate internal activity independent of environmental stimuli. Internally generated states may bring about distinct cortical processing modes. To investigate how brain state impacts cortical circuitry, we recorded intracellularly from the same neurons, under anesthesia and subsequent wakefulness, in rat barrel cortex. In every cell examined throughout layers 2-6, wakefulness produced a temporal pattern of synaptic inputs differing markedly from those under anesthesia. Recurring periods of synaptic quiescence, prominent under anesthesia, were abolished by wakefulness, which produced instead a persistently depolarized state. This switch in dynamics was unaffected by elimination of afferent synaptic input from thalamus, suggesting that arousal alters cortical dynamics by neuromodulators acting directly on cortex. Indeed, blockade of noradrenergic, but not cholinergic, pathways induced synaptic quiescence during wakefulness. We conclude that global brain states can switch local recurrent networks into different regimes via direct neuromodulation.
27412323
Cortical gamma band synchronization through somatostatin interneurons
Gamma band rhythms may synchronize distributed cell assemblies to facilitate information transfer within and across brain areas, yet their underlying mechanisms remain hotly debated. Most circuit models postulate that soma-targeting parvalbumin-positive GABAergic neurons are the essential inhibitory neuron subtype necessary for gamma rhythms. Using cell-type-specific optogenetic manipulations in behaving animals, we show that dendrite-targeting somatostatin (SOM) interneurons are critical for a visually induced, context-dependent gamma rhythm in visual cortex. A computational model independently predicts that context-dependent gamma rhythms depend critically on SOM interneurons. Further in vivo experiments show that SOM neurons are required for long-distance coherence across the visual cortex. Taken together, these data establish an alternative mechanism for synchronizing distributed networks in visual cortex. By operating through dendritic and not just somatic inhibition, SOM-mediated oscillations may expand the computational power of gamma rhythms for optimizing the synthesis and storage of visual perceptions.
6574883
Cortical Enlightenment: Are Attentional Gamma Oscillations Driven by ING or PING?
The response of a neuron to sensory stimuli can only give correlational support for functional hypotheses. To experimentally test causal function, the neural activity needs to be manipulated in a cell-type-specific as well as spatially and temporally precise way. We review recent optogenetic experiments on parvalbumin-positive cortical interneurons that link modeling studies of synchronization to experimental studies on attentional modulation of gamma oscillations in primates.
18684033
Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex
The rodent primary somatosensory cortex is spontaneously active in the form of locally synchronous membrane depolarizations (UP states) separated by quiescent hyperpolarized periods (DOWN states) both under anesthesia and during quiet wakefulness. In vivo whole-cell recordings and tetrode unit recordings were combined with voltage-sensitive dye imaging to analyze the relationship of the activity of individual pyramidal neurons in layer 2/3 to the ensemble spatiotemporal dynamics of the spontaneous depolarizations. These were either brief and localized to an area of a barrel column or occurred as propagating waves dependent on local glutamatergic synaptic transmission in layer 2/3. Spontaneous activity inhibited the sensory responses evoked by whisker deflection, accounting almost entirely for the large trial-to-trial variability of sensory-evoked postsynaptic potentials and action potentials. Subthreshold sensory synaptic responses evoked while a cortical area was spontaneously depolarized were smaller, briefer and spatially more confined. Surprisingly, whisker deflections evoked fewer action potentials during the spontaneous depolarizations despite neurons being closer to threshold. The ongoing spontaneous activity thus regulates the amplitude and the time-dependent spread of the sensory response in layer 2/3 barrel cortex.
45894212
Precise long-range synchronization of activity and silence in neocortical neurons during slow-wave oscillations [corrected].
Slow-wave sleep is characterized by alternating periods of activity and silence in corticothalamic networks. Both activity and silence are stable network states, but the mechanisms of their alternation remain unknown. We show, using simultaneous multisite intracellular recordings in cats, that slow rhythm involves all neocortical neurons and that both activity and silence started almost synchronously in cells located up to 12 mm apart. Activity appeared predominantly at the area 5/7 border and spread in both anterior and posterior directions. The activity started earlier in fast-spiking cells and intrinsically bursting cells than in regular-spiking neurons. These results provide direct evidence for two mechanisms of active state generation: spread of activity from a local focus and synchronization of weaker activity, originating at multiple locations. Surprisingly, onsets of silent states were synchronized even more precisely than the onsets of activity, showing no latency bias for location or cell type. This most intriguing finding exposes a major gap in understanding the nature of state alternation. We suggest that it is the synchronous termination of activity and occurrence of silent states of the neuronal network that makes the EEG picture during slow-wave sleep so characteristic. Synchronous onset of silence in distant neurons cannot rely exclusively on properties of individual cells and synapses, such as adaptation of neuronal firing or synaptic depression; instead, it implies the existence of a network mechanism. Revealing this yet unknown large-scale mechanism, which switches network activity to silence, will aid our understanding of the origin of brain rhythms in normal function and pathology.
207218383
Somatosensory Cortex Plays an Essential Role in Forelimb Motor Adaptation in Mice
Our motor outputs are constantly re-calibrated to adapt to systematic perturbations. This motor adaptation is thought to depend on the ability to form a memory of a systematic perturbation, often called an internal model. However, the mechanisms underlying the formation, storage, and expression of such models remain unknown. Here, we developed a mouse model to study forelimb adaptation to force field perturbations. We found that temporally precise photoinhibition of somatosensory cortex (S1) applied concurrently with the force field abolished the ability to update subsequent motor commands needed to reduce motor errors. This S1 photoinhibition did not impair basic motor patterns, post-perturbation completion of the action, or their performance in a reward-based learning task. Moreover, S1 photoinhibition after partial adaptation blocked further adaptation, but did not affect the expression of already-adapted motor commands. Thus, S1 is critically involved in updating the memory about the perturbation that is essential for forelimb motor adaptation.
206529164
Motor Control by Sensory Cortex
By a Whisker Every student learns that the sensory cortex is used for processing sensation and the motor cortex is used for perceiving movement. However, in the real world, this may not always be so neatly arranged. Matyas et al. (p. 1240) have found that sensory and motor fields are specialized for different types of movement, such that in mice the motor cortex controlled the forward movement (protraction) of their whiskers and the sensory cortex controlled backwards movements (retraction) of whiskers. So if a whisker hits an object, then a reasonable first reaction might be a motor command for retraction. Similarly, the motor cortex stimulates protraction for more active exploration. Hence, the sensory cortex is also motor and the motor cortex is also sensory. In an ecological context, these combined reactions offer a repertoire useful for a mouse seeking food and shelter in a complex environment. Mouse whisker movements are controlled by both the sensory and motor cortex. Classical studies of mammalian movement control define a prominent role for the primary motor cortex. Investigating the mouse whisker system, we found an additional and equally direct pathway for cortical motor control driven by the primary somatosensory cortex. Whereas activity in primary motor cortex directly evokes exploratory whisker protraction, primary somatosensory cortex directly drives whisker retraction, providing a rapid negative feedback signal for sensorimotor integration. Motor control by sensory cortex suggests the need to reevaluate the functional organization of cortical maps.
133982
Dynamic spike threshold reveals a mechanism for synaptic coincidence detection in cortical neurons in vivo.
Cortical neurons are sensitive to the timing of their synaptic inputs. They can synchronize their firing on a millisecond time scale and follow rapid stimulus fluctuations with high temporal precision. These findings suggest that cortical neurons have an enhanced sensitivity to synchronous synaptic inputs that lead to rapid rates of depolarization. The voltage-gated currents underlying action potential generation may provide one mechanism to amplify rapid depolarizations. We have tested this hypothesis by analyzing the relations between membrane potential fluctuations and spike threshold in cat visual cortical neurons recorded intracellularly in vivo. We find that visual stimuli evoke broad variations in spike threshold that are caused in large part by an inverse relation between spike threshold and the rate of membrane depolarization preceding a spike. We also find that spike threshold is inversely related to the rate of rise of the action potential upstroke, suggesting that increases in spike threshold result from a decrease in the availability of Na(+) channels. By using a simple neuronal model, we show that voltage-gated Na(+) and K(+) conductances endow cortical neurons with an enhanced sensitivity to rapid depolarizations that arise from synchronous excitatory synaptic inputs. Thus, the basic mechanism responsible for action potential generation also enhances the sensitivity of cortical neurons to coincident synaptic inputs.