# Consequences of Perinatal Nicotine Exposure on Functional Brainstem Development

> **NIH NIH F31** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $24,824

## Abstract

PROJECT SUMMARY
Prenatal exposure to cigarette smoke increases the risk of sudden infant death syndrome as well as
developmental deficits in the brain that persist into adulthood. Sensory impairments have been observed, notably
in the auditory system, following prenatal cigarette exposure. Due to the increasing popularity of e-cigarettes,
the need for research into prenatal exposure to nicotine alone is becoming increasingly important. The critical
period of mouse auditory development occurs after birth, allowing for perinatal nicotine exposure to accurately
model prenatal nicotine exposure on auditory system phenotypes. In PNE models, disrupted glutamatergic
signaling in the auditory cortex and impaired temporal processing in an auditory startle test has been reported.
However, the cellular mechanisms whereby perinatal nicotine exposure (PNE) impairs auditory development
and central auditory processing are currently unknown. In the auditory system, cholinergic signaling is necessary
for peripheral and central auditory processes. Recent work demonstrates the importance of nicotinic
acetylcholine receptors in signal-in-noise detection in the medial nucleus of the trapezoid body (MNTB) of the
auditory brainstem. The alpha 7 nicotinic acetylcholine receptor (α7 nAChR), essential for glutamatergic synapse
development in the hippocampus and cortex, is highly expressed in the MNTB during early postnatal
development. Utilizing the large glutamatergic Calyx of Held synapse of the MNTB, the proposed studies aim to
investigate the effect of PNE on structural and functional development of the calyx terminal, MNTB synapse, and
central auditory processing. The central hypothesis is that PNE increases α7 nAChR expression and its chronic
activation impairs glutamatergic synapse development in the MNTB resulting in central auditory deficits. Due to
the crucial role of MNTB in binaural processing, it is important to examine how the MNTB is affected by PNE
during auditory development to understand auditory processing disorders in children prenatally exposed to
nicotine. Aim 1 examines developmental expression of nAChRs at the calyx-MNTB synapse and the effect of
PNE on nAChR expression using patch-clamp electrophysiology, immunohistochemistry, and western blot. Aim
2 investigates the developmental impact of PNE on the structure and function of calyx of Held synapse. Direct
presynaptic recordings of the calyx terminal will measure vesicular glutamate release followed by 3D
reconstruction of the calyx to quantify structural development. Patch clamp recordings of the MNTB neuron with
afferent fiber stimulation will be done to measure glutamate-mediated currents, and immunohistochemistry will
visualize glutamate receptors in the calyx synapse. Aim 3 tests auditory processing following PNE using in vivo
auditory tests. The proposed aims will reveal cellular and circuit-level mechanisms underlying developmental
nicotine exposure-induced auditory deficits that will be us...

## Key facts

- **NIH application ID:** 10877710
- **Project number:** 5F31DC021102-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Mackenna Wollet
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $24,824
- **Award type:** 5
- **Project period:** 2023-07-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877710

## Citation

> US National Institutes of Health, RePORTER application 10877710, Consequences of Perinatal Nicotine Exposure on Functional Brainstem Development (5F31DC021102-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10877710. Licensed CC0.

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