Investigation of Anterior Cingulate Cortex Contributions to Hippocampal Cognitive Control

Project Abstract
Properly navigating our daily lives necessitates the judicious use of our limited cognitive resources to yield a
desired outcome. This ability, known as cognitive control, has been demonstrated in humans to depend heavily
on brain regions in the prefrontal cortex, including the anterior cingulate cortex, which is involved in effortful
decision making and performance monitoring. The hippocampus has also been implicated in cognitive control
function, particularly when the task depends on prior experience. Single-unit recordings of hippocampal neurons
have revealed a coordinated cognitive control signal that predicts cognitive control behavior. The mechanism of
cognitive control, and which brain regions contribute to it remains unclear, but the anterior cingulate is the most
likely candidate. Aim 1 will explore prefrontal cognitive control representations by using in-vivo single photon
calcium imaging to record populations of neurons within the anterior cingulate cortex (ACC) while rats perform
an active place avoidance task. This is a navigation based cognitive control task that will enable us to determine
if ACC also expresses a cognitive control signal, like in the signal in hippocampus. Whether or not a similar signal
exists does not preclude its involvement in cognitive control. Therefore Aim 2 will selectively inactivate ACC
using inhibitory chemogenetics (DREADDs) during the cognitive control task to test for necessity during various
behavioral phases. We will also record population neuronal activity from hippocampus CA1 during the
manipulations to evaluate the influence of cingulate inactivation on the hippocampal cognitive control signal.
Results from this research will reveal how cognitive control is represented in ACC and how this activity influences
hippocampal cognitive control, as well as provide a basis for interpreting how dysfunction that affects executive
function (such as schizophrenia and frontotemporal dementia) impact the brain. This work furthers Goal 1 of the
National Institute of Mental Health – defining the brain mechanisms underlying complex behaviors. Only by
addressing how cognitive control is represented and coordinated across multiple diverse brain regions can we
begin to construct a wholistic understanding of complex brain functions and mental illness.

Grant Number: 5F32MH135680-03
NIH Institute/Center: NIH
Principal Investigator: Garrett Blair