Most physiological studies in the primary auditory cortex (Al) have focused on neural spike output. However, to understand the processing and computation performed by auditory cortical neurons, it is necessary to examine the synaptic mechanisms underlying cortical response properties, i.e. to correlate the synaptic inputs of cortical cells with their outputs under various sound stimuli. In our pilot studies, we have developed techniques of in vivo whole-cell recording from auditory cortical neurons, as to establish a fundamental understanding of the synaptic connection basis for cortical responses. Here, I propose to systematically characterize the synaptic inputs, in terms of both excitatory and inhibitory inputs, underlying the frequency tuning and the supra-/sub-threshold structure of the frequency-intensity tonal receptive fields (TRFs) of single A1 neurons. In Aim 1, I will address how the tonal inputs are represented by a single Al neuron. I will determine the spatial relationship between supra- and sub-threshold TRFs of single A1 neurons, by recording tone-evoked membrane potential responses with in vivo whole-cell current-clamp method, and also characterize the change of subthreshold TRFs with the characteristic frequencies (CFs) of A1 neurons. In Aim 2, I will determine the role of spectrotemporal interaction between excitatory and inhibitory synaptic inputs in shaping the frequency tuning and TRFs of Al neurons. TRFs of pure excitatory and inhibitory synaptic inputs will be derived by using in vivo-whole-cell voltage-clamp recording. In particular, I will determine the role of the cortical inhibition in shaping the frequency tuning and TRFs. In Aim 3, I will characterize the contributions of thalamocortical and intracortical components to the excitatory synaptic TRFs of single A1 neurons by exploiting pharmacological approaches to silent the intracortical connections. With the understanding of the origins of the excitatory inputs, a basic model of synaptic input circuits underlying the TRFs of A1 neurons will be constructed. As a starting point, this project will specifically target the histologically determined excitatory pyramidal neurons in the input layers (layer 3-4) of adult rat A1. This study will be a direct extension of our pilot studies, and will generate information essential for understanding the cortical mechanisms underlying sound processing and representation in the auditory cortex. Taken together, the application of whole-cell recording technique in these studies will provide unique opportunities to address the fundamental issues concerning the mechanisms underlying auditory cortical responses, and are also likely to yield new level of information to the understanding of physiology and pathology of the auditory cortex.