# The effect of brain derived neurotrophic factor on presynaptic function

> **NIH NIH F30** · VANDERBILT UNIVERSITY · 2022 · $32,007

## Abstract

PROJECT SUMMARY
 Brain derived neurotrophic factor (BDNF) is a prevalent neurotrophin that modulates synaptic physiology
and plasticity in the central nervous system. Multiple lines of evidence point towards its involvement in mental
health disorders such as depression and schizophrenia, as well as the biological basis for an antidepressant
effect. Yet despite its demonstrated involvement in neuropsychiatric diseases, very few studies have investigated
how BDNF affects the presynaptic terminal, despite it being a fundamental component of neurotransmission.
This is in part due to the difficulty of studying the presynapse and the lack of available technology to do so until
more recently. Previously published work using viral manipulation in hippocampal slices demonstrates that BDNF
acts upon the high affinity TrkB receptor at the presynapse to increase release probability, or the likelihood that
a vesicle will be release in response to an action potential. With the resulting hypothesis that BDNF signaling
specifically targets presynaptic function via TrkB signaling pathways, this proposal aims to investigate the
molecular basis of BDNF’s effect at the presynapse. This will be done through the following: first, examining the
effect of BDNF on excitatory neurotransmission (subaim 1.1). Preliminary data from subaim 1.1 show that in
dissociated hippocampal cultures, release probability at excitatory synapses is increased in response to acute
BDNF treatment in a manner dependent on TrkB activation. Subaim 1.2 will dissect the potential mechanisms
underlying this effect through using pharmacological approaches to screen for potential downstream pathways
that are involved in this effect. Because the spatiotemporal context of BDNF activity is critical in its effect, I will
also use cTrkB KO hippocampal cultures to examine the spontaneous and evoked release events as a result of
endogenous BDNF manipulation (subaim 1.3). Local calcium transients at synapses are strongly linked to
neurotransmitter release, especially evoked release. I will thus investigate how presynaptic calcium transients
are affected by exogenous BDNF (subaim 2.1), endogenous BDNF using cTrkB cultures (subaim 2.2), and
whether BDNF utilizes calcium to modulate neurotransmission (subaim 2.3). The proposed studies will involve
optical imaging of in vitro neuron cultures transfected or infected with fluorescent probes to study the presynase,
as well as pharmacological and genetic manipulation tools to provide further mechanistic insight into findings.
This research will further current understanding of the fundamental role of BDNF at the synapse, with implications
for improving current therapeutics such as for antidepressants. The proposed research will be accomplished
through a thoughtfully developed training plan that involves opportunities to further critical thinking skills,
technical expertise, and scientific communication. Additionally, the research environment provided by the MSTP,
Va...

## Key facts

- **NIH application ID:** 10534078
- **Project number:** 1F30MH127808-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Camille Wang
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $32,007
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534078

## Citation

> US National Institutes of Health, RePORTER application 10534078, The effect of brain derived neurotrophic factor on presynaptic function (1F30MH127808-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10534078. Licensed CC0.

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