# The role of excitatory VTA projections in novelty-dependent behavior

> **NIH NIH R01** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2024 · $365,310

## Abstract

PROJECT SUMMARY
Learning and memory involve multiple brain areas. However, the hippocampus (CA1) and ventral tegmental area
(VTA) are the brain regions primarily involved in novelty detection and context discrimination. Abnormal
connection between these brain regions leads to deficits in novelty behavior. For decades, the function of the
VTA-CA1 circuit in learning, and the dysregulation of midbrain neurotransmitter systems in diseases like
schizophrenia, depression, and addictions have been attributed (primarily) to the dopamine neurons. Because
of this traditional focus on the midbrain dopaminergic systems, the glutamate pathway has been overlooked and
is less understood in normal brain function and neuropsychiatric disorders. In a recent study, we showed that
the VTA glutamate terminals are anatomically dominant in the CA1 while VTA dopamine terminals were limited
to the basal dendrite layer. Functional tracing of the VTA-CA1 pathway shows that selective activation of VTA
glutamate and dopamine neurons has distinguishable effects on CA1 local circuits. Photostimulation of VTA
glutamate – but not the dopamine – neurons increased burst firing of CA1 pyramidal cells. Likewise, stimulation
of the VTA glutamate pathway increased putative pyramidal cells (PYR) excitation of interneurons (INT) in CA1
ensembles. In freely behaving mice, novelty detection tasks that activate the VTA-CA1 circuit increased CA1
PYR/INT connectivity while its inhibition altered novelty-linked behavior. Based on preliminary results, the
proposed research will elucidate the functional significance of the VTA glut→CA1 tract in the hippocampal
encoding of novelty-dependent behavior including context discrimination and habituation. The results of the
proposed research will increase our understanding of VTA excitatory modulation of cognitive processes and
control of adaptive behavior.

## Key facts

- **NIH application ID:** 10890872
- **Project number:** 5R01MH132018-02
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Olalekan Michael Ogundele
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $365,310
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890872

## Citation

> US National Institutes of Health, RePORTER application 10890872, The role of excitatory VTA projections in novelty-dependent behavior (5R01MH132018-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10890872. Licensed CC0.

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