Project Summary/Abstract There is considerable evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply operations of the same form, but we lack a theoretical framework for how such canonical neural circuit computations can support a wide variety of cognitive processes and brain functions. Through the proposed research, we aim to provide one. Preliminary results demonstrate that a family of circuit models, called Oscillatory Recurrent Gated Neural Integrator Circuits (ORGaNICs), simulates many key neurophysiological and cognitive/perceptual phenomena. We propose to develop models of the dynamics of attention, and working memory, and to test those models with previously published datasets acquired with a wide range of methodologies: human behavioral data, neurophysiological data from primate and rodent prefrontal cortex (PFC), electrophysiology and Ca2+ imaging data from rodent prefrontal cortex, and electrophysiology data from rodent medial entorhinal cortex. In Aim 1, we hypothesize that normalization is critical for the stability and robustness of the recurrent circuits that underlie working memory. We will test this hypothesis by developing an analytical theory, based on ORGaNICs, of delay-period activity, and fitting published measurements of response dynamics in PFC. In Aim 2, we hypothesize that behavioral performance during working memory tasks is limited by trial-to-trial variability in delay-period activity, and also that top-down signals from working memory circuits provide the attention-control signals that modulate sensory activity in visual cortex. We will test these hypotheses by developing an analytical theory of attention and working memory, combining a visual cortex model and a PFC model, and using it to fit previously published measurements of behavioral performance from a variety of attention and working-memory experiments. In Aim 3, we propose to develop and test a theory of manipulation in working memory, with application to navigation, specifically using ORGaNICs to model the responses of populations of head-direction cells while animals are performing the active place avoidance task. We hypothesize that head-direction cells in MEC operate like a working memory representation, by encoding a “landmark” (a sensory feature) relative to the animal's current head direction, and then updating/manipulating the representation of that landmark as the animal's orientation changes. We will test key predictions of the theory with new experiments. The proposed research has the potential to be transformative by: providing a new set of analytical results and computational (software) tools for characterizing and simulating a broad range of neural circuit models, which will impact experimental design and data analysis; making new experimentally-testable predictions for both ORGaNICs and alternative models; and testing some of those predictions with new experiments.

Project Narrative There is increasing recognition that many neurological and psychiatric illnesses are dysfunctions of neural circuit computation. But we lack a theoretical framework for how such neural circuit computations function to support a wide variety of cognitive processes. Through the proposed research, we aim to provide such a theory, thereby providing a better understanding of the details of how brain circuits operate, leading to better assessment, diagnosis, and treatment of a wide range of brain disorders.