# Gene Expression Programs in Maturing Dopamine Neurons: Temporal Regulation, Subcellular Localization, and Alteration by Amphetamine

> **NIH NIH F30** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $51,036

## Abstract

Early initiation of drug use is associated with long-term poor social outcomes and higher rates of substance
use disorders in adulthood. Altered dopamine (DA) neurotransmission in forebrain circuits is a hallmark of drug
addiction and DA inputs to these circuits continue to mature into adolescence. Recent evidence suggests that
adolescent drug exposure alters DA axonal maturation and disrupts proper forebrain development, resulting in
persistent behavioral alterations that may increase the risk of drug addiction. In order to prevent long-term
adverse outcomes related to adolescent drug use, we must understand the mechanisms by which drugs of
abuse alter normal development of DA neurons. Postnatal development of DA neurons is complex: a small
number of DA neurons must survive two rounds of cell death and mature their axonal innervation in expansive
forebrain structures, suggesting tight regulation of developmental gene expression programs. These DA
neuron developmental programs may be particularly susceptible to amphetamine, a psychostimulant drug of
abuse that causes lasting changes in forebrain DA innervation when administered during early adolescence.
This proposal will develop a precise understanding of gene expression in DA neurons across postnatal
development and will analyze how early adolescent amphetamine exposure alters normal gene expression
patterns. A combination of neuroanatomical, biochemical, next-generation sequencing, and systems biology
approaches will be applied to a transgenic mouse that enables DA neuron-specific, genome-wide analysis of
translating mRNAs. Aim 1 will identify changes in gene expression associated with 1) key transitional
timepoints related to axonal growth and cell death in early postnatal development and 2) response to
adolescent amphetamine exposure and prolonged axonal maturation during later postnatal development. Cell
type-specific expression data will be used to elucidate and validate master regulator genes controlling DA
neuron maturation. Aim 2 will explore the role of subcellular mRNA localization and protein synthesis in
maturing DA neurons across the same conditions studied in Aim 1 (i.e., across postnatal development and
following amphetamine exposure). The proposed research will enhance our understanding of DA neuronal cell
biology and will have far reaching implications for the neurodevelopmental origins of drug addiction. This pre-
doctoral fellowship will support rigorous scientific training of the applicant at Columbia University Medical
Center. An interdisciplinary mentorship team with unique expertise will provide training in both neuroscience
and systems biology, enhancing the applicant’s technical skills and professional development. The applicant
will also undergo extensive clinical training, refining general clinical skills and providing field-specific exposure
relevant to the applicant’s interest in neuropsychiatry. The activities proposed under this award will provide the
applicant wi...

## Key facts

- **NIH application ID:** 10085218
- **Project number:** 5F30DA047775-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Benjamin Hobson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-01-15 → 2024-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085218

## Citation

> US National Institutes of Health, RePORTER application 10085218, Gene Expression Programs in Maturing Dopamine Neurons: Temporal Regulation, Subcellular Localization, and Alteration by Amphetamine (5F30DA047775-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10085218. Licensed CC0.

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