# Examining the neural substrates of reward in the lateral septum

> **NIH NIH F31** · EMORY UNIVERSITY · 2023 · $47,694

## Abstract

PROJECT SUMMARY
The lateral septum (LS) is an enigmatic brain region that contributes to a multitude of behaviors and
has been implicated in a number of psychiatric disorders including anxiety. Over many decades,
researchers have attempted to ascertain how this one brain region gives rise to such functional
diversity. However, the results of these studies have often been contradictory. Early studies of the LS
divided it into distinct anatomical subregions, suggesting a putative role for its subregions in mediating
different functions. Recent research has revisited this earlier work and postulates that there are
functional subunits within the LS, which may be selecting for different behavioral outcomes. This
proposal seeks to address this theory by characterizing the anatomical organization, neural encoding
properties, and function of two LS projection populations. In particular, I will focus on two target regions
that receive input from the lateral septum and exemplify the functional diversity of the LS: the ventral
tegmental area (VTA) known for its role in reward representation and the bed nucleus of the stria
terminalis (BNST) known for its role in cue encoding. In Aim 1, I will perform projection-specific cellular
resolution calcium imaging during a series of operant behavioral paradigms to evaluate the role of each
projection population in reward-related behavior. I hypothesize that each projection population will
encode distinct task features, contributing to the functional diversity of the LS. Thus, I predict that the
LS-VTA will encode reward-related information and the LS-BNST will encode reward cues. In Aim 2, I
will use projection-specific, closed-loop optogenetic manipulations to determine the causal role of the
LS-VTA and LS-BNST projection populations in different trained reward-related behaviors. I will
quantify the effects of inhibition of these two populations on different behavioral outcomes on an operant
assay, which will provide insight into how these LS subpopulations are functionally distinct. The results
from this proposal will provide a more complete view of how the LS functions, specifically in reward-
related behaviors. It will further our understanding of a brain region that has evaded explanation for
many years and may prove to be a crucial target for the treatment of various psychiatric disorders.

## Key facts

- **NIH application ID:** 10751657
- **Project number:** 1F31MH133373-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jennifer Samantha Isaac
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-08-11 → 2026-08-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751657

## Citation

> US National Institutes of Health, RePORTER application 10751657, Examining the neural substrates of reward in the lateral septum (1F31MH133373-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10751657. Licensed CC0.

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