Inhibitory neurons in the cortex are thought to influence multiple types of cortical activity, ranging from sensory processing to pathological states such as epilepsy and neuropsychiatric illnesses. There are multiple types of inhibitory interneurons in the cortex, but the role(s) of each type is not clear. This grant will investigate one of these, known as the "low-threshold spiking" (LTS) cells, which have some characteristics that suggest some things about their function: a) initial response to input from cortical excitatory cells is weak, but facilitates greatly during a stimulus train, b) LTS cells are strongly electrically coupled exclusively to other LTS neurons, and c) LTS neurons can mediate wide-spread synchronous cortical activity. These characteristics suggest that LTS cells may have a wide-spread influence on strong, ongoing cortical activity rather than causing brief, local stimulus-locked inhibition. These neurons will be studied using whole-cell patch clamp techniques by recording synaptically coupled pairs of neurons in layer IV of the somatosensory cortex (SI) in thalamocortical slices from mice that express green fluorescent protein in LTS cells. These experiments will 1) resolve whether cortical LTS neurons in mice receive direct thalamic input, 2) determine what types of thalamic stimuli can activate LTS cells (whether by mono- or polysynaptic pathways), and 3) show whether the neuromodulator norepinephrine affects the involvement of LTS neurons in cortical activity.