# Impact of BDNF on the Development of Social Behavior Circuits

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $618,928

## Abstract

Project Summary
Social behavioral impairments are common and highly disabling symptoms in many psychiatric disorders,
including depression and anxiety disorders that emerge in adolescence and young adulthood. The intrinsic
complexity of social behavioral outcomes have made understanding their underlying neural correlates difficult.
In particular, the molecular mechanisms regulating the development and function of social behavioral circuits
remain largely unknown. In this context, one potential candidate molecule is brain-derived neurotrophic factor
(BDNF), a key regulator of neuronal synaptic plasticity that has been implicated in depression and anxiety
disorders, and is also highly expressed in brain regions implicated in social behaviors. Our central hypothesis is
that BDNF is required for the proper development during a peri-adolescent timeframe of a key orbitofrontal cortex
(OFC)-to-amygdala circuit that supports social approach behavior. Multiple studies in rodents, non-human
primates, and humans indicate that the OFC supports cost-benefit decision making, and encodes and updates
representations of the expected value of future outcomes, suggesting that the OFC may play a role in motivating
social approach behavior. Our extensive preliminary data in loss-of-function BDNF mouse lines support the
premise of the requirement of BDNF in the peri-adolescent development of OFC-amygdala circuits related to
social function. We propose to assess the impact of BDNF on the structural and functional development of this
OFC-to-amygdala circuit during the peri-adolescent period. We will use a live calcium imaging technique (fiber
photometry) to record the activity of this circuit during a repertoire of social behaviors. In addition, we will use
chemogenetic tools to bi-directionally modulate the activity of these neurons and to delineate more precisely
what aspects of social behavior are mediated by these OFC projections. Finally, we will utilize newly developed
viral reagents for circuit-specific and developmentally-timed manipulations of BDNF signaling. Our studies are
designed identify a new role for BDNF during peri-adolescence to establish optimal function of cortico-amygdala
circuits related to social behaviors.

## Key facts

- **NIH application ID:** 9998176
- **Project number:** 1R01MH123154-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Francis Sang Yong Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $618,928
- **Award type:** 1
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998176

## Citation

> US National Institutes of Health, RePORTER application 9998176, Impact of BDNF on the Development of Social Behavior Circuits (1R01MH123154-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998176. Licensed CC0.

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