DESCRIPTION (provided by applicant): Electrical synapses are specialized connections, comprising gap junctions,that allow ionic current and small organic molecules to pass from one neuron to another. Only in the past few years has it become clear that electrical synapses are a major feature of the neuronal circuitry across the mammalian central nervous system. The PI's research has shown that electrical synapses are common between inhibitory neurons of the neocortex and thalamus, and that the protein connexin36 is necessary for these connections. This investigation will characterize the functions and the regulation of electrical synapses in the thalamus and neocortex. There are three specific aims: 1) the distribution of electrical synapses in both inhibitory and excitatory neurons of the thalamocortical system will be characterized in detail using electrophysiological, anatomical, and molecular methods; 2) the hypothesis that electrical synapses can coordinate the activity of inhibitory interneuron networks, and the excitatory neurons they contact, will be tested under controlled conditions in thalamus and neocortex; 3) the hypothesis that electrical synapses can be modulated by neural activity, neurotransmitters, and intracellular signaling systems will be tested in thalamus and neocortex. This investigation will provide a deeper understanding of the properties and functions of electrical synapses, a newly recognized feature of the mammalian forebrain.