# Neurohypophyseal regulation of midbrain dopamine systems.

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $395,000

## Abstract

The brain is composed of intricate circuits of neurons communicating via fast electrical signals created by the
coordinated actions of excitatory and inhibitory neurotransmission. Overlaid on this broad structure is a diverse
set of slower instructive chemical signaling, referred to collectively as neuromodulation, which critically regulate
fast transmission and neuronal function. This proposal brings together molecular-genetic tools, expertise in
manipulating and interrogating neuromodulatory neuronal circuits, imaging and electrophysiology to decipher
neurohypophyseal regulation of dopaminergic neurons. Dopamine is an essential modulator, required for
vertebrate life. Dopamine dysregulation, best studied in degenerative disease, is also associated with anxiety
and mood disorders, as well as neurodevelopmental diseases and addiction. Oxytocin, a neurohypophyseal
hormone and neuromodulator implicated in social affect and reproductive behaviors, interacts with reward
systems indirectly, and also by directly regulating the tonic activity of dopamine neurons, as work from our
laboratory has recently demonstrated. The control of dopamine signaling by neurohypophyseal peptides
represents a powerful regulation of essential adaptive behaviors, which both emphasizes the central
importance of these endogenous peptides in development and establishes them as therapeutic targets for
ameliorating disease states. The objective for this proposal is to build on our preliminary data in order to better
understand the mechanisms and context of direct neurohypophyseal control over DA neuron function. The
major overall premise of this proposal is that neurohypophyseal peptides act centrally in midbrain
dopaminergic regions regulating cellular activity, synaptic transmission, as well as plasticity, and that this
regulation is sex-independent and important in early development. To address several hypotheses deriving
from this premise, we synthesize anatomical, electrophysiological, and behavioral assays, with technical
innovations ranging from new light-sheet imaging technologies to promoter-driven viruses for orthogonal
control of multiple modulatory systems. Carrying out the proposed experiments would advance our conceptual
understanding of the complex neuromodulatory systems regulating affect and reward, and it is relevant to
numerous mental health, neurodevelopmental and neurodegenerative disorders characterized by dysfunctional
neuromodulation.

## Key facts

- **NIH application ID:** 10176186
- **Project number:** 5R01MH117111-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** YEVGENIA KOZOROVITSKIY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2018-08-13 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176186

## Citation

> US National Institutes of Health, RePORTER application 10176186, Neurohypophyseal regulation of midbrain dopamine systems. (5R01MH117111-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176186. Licensed CC0.

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