Circuit Mechanisms Underlying Persistent Activity in a Neural Integrator

Abstract
Short-term memory function is commonly supported through persistent activity, the sustained
response of populations of neurons following the offset of a memorized stimulus. This form of
activity underlies diverse tasks including navigation, motor control, and decision-making. Classic
mechanistic theories have idealized such activity through models that assume strongly
homogeneous populations of neurons that encode only a single variable and generate perfectly
stable patterns of activity. This contrasts with recent work showing that neurons in real biological
memory networks exhibit multiplexed encoding of multiple stimulus attributes, temporally varying
responses across the population, and context dependence. Here we address the circuit
mechanisms and role of this diversity in function through a combined experimental-theoretical
approach. Experiments are conducted in a short-term memory circuit of the larval zebrafish gaze
control system that contributes to stable vision by precisely maintaining the eyes on a visual
target. Taking advantage of the quantitative precision and experimental tractability of this system,
we combine whole-circuit, synapse-resolution anatomy with circuit-wide recordings and
perturbations of activity at cellular resolution. In Aim 1, we combine these data into a model of the
system in which neurons map in a one-to-one manner with experimentally recorded neurons. This
enables us to infer the interactions within and between neurons of different anatomical, genotypic,
and functional cell classes and form predictions for how these interactions govern circuit function.
In Aim 2, we use 3D cellular resolution optical imaging and stimulating perturbations of neuronal
activity to refine our model and test model predictions. In Aim 3, we expand our capacity to form
precise characterizations of within and between cell-class interactions by developing and applying
3D suppression of neurons across the memory circuit. Altogether, this work promises to greatly
expand our understanding of the circuit mechanisms and role of cell type diversity in persistent
firing, short-term memory, and motor control.

Grant Number: 5R01EY027036-08
NIH Institute/Center: NIH
Principal Investigator: Emre Aksay