# Multimodal Characterization of Prefrontal and Premotor Circuits Underlying Perceptual Decision Making in Therhesus Monkey

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $594,620

## Abstract

Abstract: The objective of the proposed research is to understand the diverse lamina-specific neurons, and
connections between the dorsolateral prefrontal cortex (DLPFC) and the rostral aspect of the dorsal premotor
cortex (PMdr) during decision-making. Decision-making refers to our ability to choose and perform appropriate
actions based on sensory cues and context to achieve behavioral goals. Pressing the brakes to stop the car in
response to a red light or choosing what dress to wear are common decisions that we make in our everyday life.
Disrupted activity in brain areas such as the DLPFC and PMdr contribute to the impairments in decision-making
observed in mental illness. Our past work and other research has provided some insight into the involvement of
DLPFC and PMdr in decision-making and that these areas are strongly interconnected. However, we currently
do not understand 1) the relationship between biophysical properties and morphological structure, and in vivo
decision-related activity of neurons in different layers of these brain areas, and 2) whether the connections
between DLPFC and PMdr are feedforward, feedback or lateral (both feedforward and feedback). We address
these open questions by using a multimodal approach that combines in vivo neurophysiology in DLPFC and
PMdr of behaving monkeys, decoding and granger causality analysis, optical stimulation of DLPFC inputs to
PMdr, tract tracing experiments and in vitro single neuron electrophysiology and morphometry in slices from the
same subjects. Our first aim uses laminar multi-contact electrodes to investigate neuronal responses across
layers of PMdr, and DLPFC while monkeys perform a novel decision-making task that separates perceptual
decisions from action selection. We will investigate if in vivo differences are related to differences in biophysical
and morphological properties of these neurons with in vitro whole-cell patch-clamp recordings of lamina-specific
neurons in PMdr slices. In Aim 2, we examine the granger causality between the local field potentials recorded
simultaneously in DLPFC and PMdr to understand whether DLPFC sends a feedforward driving input or a
modulating feedback input. We combine these in vivo experiments with anatomical tracing experiments in
DLPFC to understand the bidirectional laminar pattern of DLPFC and PMdr connections. In Aim 3, we will inject
an opsin in DLPFC and stimulate the anterograde fibers in PMdr in vivo to causally investigate whether the
pattern of activity induced in PMdr by stimulation of DLPFC is consistent with feedforward, feedback, or lateral
connections. To obtain a more detailed understanding of the pattern of inputs from DLPFC to PMdr, we will
investigate in vitro synaptic responses of these PMdr neurons in layers 3 and 5 to optical stimulation of afferent
DLPFC fibers and localize the morphological compartments of PMdr neurons to which DLPFC afferent fibers
provide inputs. Impact: This project will elucidate the in vivo and in...

## Key facts

- **NIH application ID:** 10864977
- **Project number:** 5R01NS122969-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Chandramouli Chandrasekaran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $594,620
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864977

## Citation

> US National Institutes of Health, RePORTER application 10864977, Multimodal Characterization of Prefrontal and Premotor Circuits Underlying Perceptual Decision Making in Therhesus Monkey (5R01NS122969-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10864977. Licensed CC0.

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