# Regulation of synaptic plasticity by BDNF-endocannabinoid interactions

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2023 · $541,075

## Abstract

PROJECT SUMMARY
The goal of this project is to explore the functional relevance of interactions between brain-derived neurotrophic
factor (BDNF) and endogenous cannabinoids (eCB) in regulating activity-dependent synaptic plasticity in the
neocortex and hippocampus. Although there is growing evidence for crosstalk between BDNF and eCBs, little is
known regarding potential synaptic interactions. We have previously characterized the synaptic effects of eCBs
and BDNF in layer 2/3 and layer 5 of somatosensory cortex as well as the CA1 area of hippocampus, and we
have recently shown that the presynaptic effects of BDNF at cortical and hippocampal inhibitory synapses are
mediated by the BDNF-induced release of eCBs from postsynaptic pyramidal cells. We have also found that
BDNF causes release of eCBs at excitatory synapses, and this eCB signaling mitigates the direct facilitatory
effects of BDNF at these synapses. We are now poised to explore the functional relevance of these interactions
in regulating activity-dependent synaptic plasticity. In particular, we will examine the interactions between
endogenous BDNF-induced eCB release and activity-dependent eCB release in regulating the magnitude and
direction of plasticity at excitatory and inhibitory synapses. These studies will combine electrophysiology and
calcium imaging with pharmacological and genetic approaches to manipulate these signaling systems. We will
also examine these signaling interactions using mice engineered to express common human single-nucleotide
polymorphisms (SNPs) that affect either endogenous BDNF or anandamide levels. Importantly, we will carry out
parallel studies using cultured human induced pluripotent stem cell (iPSC)-derived neurons generated from
individuals who carry these same SNPs.

## Key facts

- **NIH application ID:** 10531584
- **Project number:** 5R01NS111986-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Eric S Levine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $541,075
- **Award type:** 5
- **Project period:** 2019-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10531584

## Citation

> US National Institutes of Health, RePORTER application 10531584, Regulation of synaptic plasticity by BDNF-endocannabinoid interactions (5R01NS111986-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10531584. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*