A Modeling Framework for Deriving the Structural and Functional Architecture of a Short-Term Memory Microcircuit

Abstract

Although many studies have identified neural correlates of memory, relatively little is known about the circuit properties connecting single-neuron physiology to behavior. Here we developed a modeling framework to bridge this gap and identify circuit interactions capable of maintaining short-term memory. Unlike typical studies that construct a phenomenological model and test whether it reproduces select aspects of neuronal data, we directly fit the synaptic connectivity of an oculomotor memory circuit to a broad range of anatomical, electrophysiological, and behavioral data. Simultaneous fits to all data, combined with sensitivity analyses, revealed complementary roles of synaptic and neuronal-recruitment thresholds in providing the nonlinear interactions required to generate the observed circuit behavior. This work introduces a new methodology for identifying the cellular and synaptic mechanisms underlying short-term memory, and demonstrates how the anatomical structure of a circuit may belie its functional organization.