An essential step to achieving an understanding of auditory cortical function is determining how information contained in sensory inputs is represented and processed in different individual cortical neurons. Recently, several laboratories have successfully applied a """"""""blind"""""""" in vivo whole-cell voltage-clamp recording technique to cortical neurons. This technique can resolve sensory-driven excitatory and inhibitory synaptic inputs onto the recorded neuron, making it possible to construct a synaptic connectivity model to predict the neuron's response under arbitrary sensory stimulation. Although this technique can be combined with post hoc histological methods to reconstruct the morphology of recorded cells, its """"""""blind"""""""" nature largely limits its potential in examining various cell types in the cortex, especially those that are small in size or spatially sparse; the """"""""blind"""""""" patch-clamp recording technique will normally result in a biased sampling of pyramidal neurons in the cortex. In this exploratory project, we will study a new technique for revealing functional synaptic inputs made onto different types of individual cortical neurons ? two-photon imaging guided whole-cell (TPGWC) recording ? in which fluorescence-labeled neurons are visualized by two-photon imaging and specifically targeted for patch recording. This technique has largely benefited from recent developments in mouse genetics in the labeling of specific cell types with fluorescence proteins, such as green fluorescence protein (GFP), whose expression is controlled by cell-type specific promoters. Initially, we plan to apply this recording technique to GFP-labeled GABAergic interneurons in the input layers (L3/4) of the mouse primary auditory cortex (A1), and aim at addressing two fundamental questions: a) What subthreshold/spike TRF properties are possessed by Al inhibitory neurons? b) How do cortical excitatory and inhibitory synaptic inputs determine subthreshold/spike TRF structure of A1 inhibitory neurons?
