Organization of Memory in Neural Circuits

A fundamental capacity of the mammalian cerebral cortex is to process information in a form conducive to encoding, storage and retrieval of memories. A general organizational principle of cortical memory circuits states that these steps all require a precisely orchestrated spatio-temporal interaction among a large number of relatively uniform excitatory and a numerically fewer but richly diverse population of inhibitory and neuromodulatory circuit elements. However, a mechanistic understanding of how these circuit motifs interact during elementary steps of memory processing is lacking. The goal of my laboratory is to study the functional anatomical organization of memory circuits in the rodent hippocampus and to provide a biophysically-based characterization of elementary memory processing and storage mechanisms present in individual neurons. I use high-resolution optical and electrophysiological methods together with optogenetic manipulations of specified circuit motifs in vitro, to study how dynamic interactions among excitatory, inhibitory and neuromodulatory inputs in various subcellular domains of neurons underlie information processing and storage in the hippocampal circuit. To link these elementary computations to memory functions, I apply high-resolution functional imaging in awake mice in vivo. I plan to investigate numerous fundamental questions including: (i) the role of specific spatio-temporal patterns of inhibitory and neuromodulatory inputs in determining neuronal input-output transformations, (ii) the effect of local inhibition and global neuromodulation on the dynamics of subcellular integration and compartmentalization of inputs, and (iii) regulation of various forms of synaptic and intrinsic plasticity by inhibitory and neuromodulatory inputs in the hippocampus.