# Connectivity and Function of the Asymmetric Habenulo-Interpeduncular Pathway

> **NIH NIH R37** · DARTMOUTH COLLEGE · 2024 · $498,270

## Abstract

ABSTRACT/PROJECT SUMMARY
The habenulo-interpeduncular pathway, a forebrain to midbrain conduction system in the 
vertebrate brain, has been implicated in many essential processes, from sleep to fear/anxiety, 
pain, learning, motivation, feeding, reproduction, and reward, and in pathological states such 
as mood disorders and addiction. Despite its importance and diverse roles, little is known 
about the complete repertoire of neuronal subpopulations and precise connectivity between 
the bilaterally paired dorsal habenular nuclei (dHb) of the dorsal diencephalon and their major 
target, the unpaired interpeduncular nucleus (IPN) of the ventral midbrain. A renewed interest 
in this pathway came from its association with nicotine dependence and withdrawal and from 
the discovery that, in zebrafish and other vertebrates, the dHb develop with prominent left-right differences in their size, organization, molecular properties and connections to the IPN. 
In previous work, we described an asymmetric olfactory projection to a subset of neurons in 
the right dHb that helps mediate the response to aversive cues and determined that altering 
directional asymmetry of the dHb induces behavioral and physiological changes indicative of 
enhanced fear/anxiety. Using state-of-the-art genetic, transgenic, imaging, and behavioral 
approaches, we now aim to identify all of the neuronal populations of the Hb-IPN pathway 
and further define which groups of neurons are involved in the response to negative cues. 
We have also extended our studies to characterize the pre-synaptic input and post-synaptic 
targets of this conduction system to gain a more complete understanding of the underlying 
neural circuits and their connectivity. The proposed research will shed light on a poorly 
understood yet highly conserved neural pathway and also address how differential 
processing of information by neurons on the left and right sides of the brain leads to 
appropriate behavioral responses.

## Key facts

- **NIH application ID:** 10758959
- **Project number:** 5R37HD091280-08
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** MARNIE E HALPERN
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $498,270
- **Award type:** 5
- **Project period:** 2022-12-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758959

## Citation

> US National Institutes of Health, RePORTER application 10758959, Connectivity and Function of the Asymmetric Habenulo-Interpeduncular Pathway (5R37HD091280-08). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10758959. Licensed CC0.

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