Organization and learning-associated dynamics of prefrontal synaptic connectivity

ended

How does experience alter the functional architecture of synaptic connections in neural circuits? This question is particularly pertinent for the complex circuits of the medial prefrontal cortex (mPFC), a high-order associative neocortical area that plays a crucial role in flexible, goal-directed behavior. The mPFC is densely interconnected with cortical and subcortical circuits, and its neurons were shown to undergo substantial experience-dependent structural remodeling that is thought to support learning and memory consolidation. However, little is known regarding the synaptic organization of this complex circuit, and of the functional implications of its experience-dependent structural remodeling. In this proposal, we aim to uncover the organization and learning-associated dynamics of functional connectivity in the mouse mPFC. To obtain high-resolution maps of cell type-specific synaptic connectivity in the mPFC, we will combine single-cell optogenetic manipulation with calcium imaging and electrophysiology in vitro, and establish the circuit-wide organization of connectivity within and between defined projecting neuron populations. We will test the hypothesis that pyramidal neurons projecting to subcortical targets form tightly interconnected subnetworks, and that inhibitory inputs to these networks, through selective innervation, can modulate information output from the mPFC. To understand how learning changes the functional synaptic organization of the mPFC, we will establish an all-optical system for interrogation of synaptic connectivity in vivo. We will utilize this powerful platform to test the hypothesis that prefrontal-dependent learning is associated with reorganization of local-circuit functional connectivity among identified subcortically-projecting cell assemblies. Our innovative technology will be widely applicable for neural circuit analysis in a variety of systems, and allow us to gain new insights into the complex circuitry of the mPFC.