# Molecular specification of dopaminergic neuron diversity

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $593,690

## Abstract

PROJECT SUMMARY
Dopamine is produced by a small but impactful subset of neurons in the eye and brain. Because this
neuromodulator plays a critical role in a host of mental illnesses and diseases, it is vital to understand how
dopamine neuron subsets are established and maintained. Our preliminary data show that the serine-threonine
kinase LKB1 is required to restrict the number of dopaminergic neurons in the retina. In addition, we identify
new dopaminergic cell subsets and show that LKB1 is cell-intrinsically required in inhibitory interneurons to
modulate dopamine neuron diversity using molecular and neurogenetic approaches. This is a compelling result
because factors that control the number and type of neurons that produce dopamine have remained elusive.
To understand how LKB1 regulates dopamine neuron diversity, we have devised a strategy encompassing
neural identity and connectivity mapping, cell-type specific intersectional genetic and viral strategies, molecular
and biochemical studies, and functional analysis. We propose three aims. In Aim 1, we ask whether LKB1 is
spatially and temporally sufficient to instruct dopamine neuron diversity by modulating this kinase in specific
locations and at particular times. In Aim 2, we identify the mechanism through which LKB1 functions and test
the hypothesis that LKB1-AMPK signaling plays a critical role. In Aim 3, we extend our analysis to the midbrain
to test whether LKB1 is similarly required in this disease-relevant brain region to limit dopamine neuron
diversity. Identifying a kinase pathway that precisely controls dopamine neuron diversity is surprising, so
completing these aims will markedly advance our understanding of how dopaminergic neurons are endowed
with their unique properties. In addition, these results will provide new therapeutic avenues for restoring
dopamine production in the context of disease.

## Key facts

- **NIH application ID:** 10770532
- **Project number:** 5R01EY033772-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Benjamin R Arenkiel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $593,690
- **Award type:** 5
- **Project period:** 2023-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770532

## Citation

> US National Institutes of Health, RePORTER application 10770532, Molecular specification of dopaminergic neuron diversity (5R01EY033772-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10770532. Licensed CC0.

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