# Maternal nicotine exposure and memory impairments in offspring

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $347,625

## Abstract

Cigarette smoking during pregnancy can have severe impacts on the mental and physical health of
offspring, including long-lasting impairments in IQ and memory. Still, as of 2010 an estimated 12.3% of
expectant mothers in the United States continued smoking. Cigarette smoke has been shown to contain
more than 8,000 chemicals, but among these nicotine is thought to be the leading neuroteratogen. Several
studies using rodent models of perinatal nicotine treatment have demonstrated that exposure to nicotine
during early development causes long-lasting deficits in learning and memory. However, the outstanding
question in the field remains which cellular and molecular changes induced by nicotine underlie this
cognitive impairment.
The first two weeks of postnatal development of rodents, which is roughly equivalent to the third trimester of
human development, is a critical time for neurogenesis and synaptogenesis in the hippocampus, a brain
region associated with memory formation. In order to identify long-lasting cellular, molecular and circuitry
changes in the hippocampus that may underlie nicotine-induced cognitive impairments, we use a model of
early postnatal nicotine exposure in rodents that targeted this critical period of hippocampal development.
We have tested our model to show that it results in impaired memory, and used electrophysiological,
pharmacological and voltage sensitive dye imaging techniques to identify nicotine-induced changes in
hippocampal function. We found several changes in hippocampal network activity, synaptic plasticity and
nicotinic modulation of hippocampal function, all associated with the α2 nicotinic acetylcholine receptor
(nAChR) subtype, that could be the cause of memory deficits.
The α2* nAChR, the most sparsely expressed nAChR subtype in the brain, has long been ignored in the
study of nicotine's central action. However, we have shown that this subtype, which is selectively expressed
in GABAergic interneurons in the stratum oriens/alveus, is an important component in the hippocampal
circuitry gating information flow and long-term potentiation (LTP; considered to be a cellular substrate of
learning and memory). Furthermore, our results suggest the importance of α2* nAChRs in hippocampus-
dependent memory, and lay the foundation for further studies of the mechanisms underlying cognitive
impairment after maternal smoking. In the research proposed here, we will test the hypotheis that
developmental nicotine exposure, by inappropriately activating α2* nAChRs, causes functional alterations of
α2* nAChRs-expressing interneurons, and that these changes could be tied to maternal-nicotine-induced
hippocampal memory impairments. Our major goals are to determine whether the α2* nAChR indeed plays
a causal role in maternal-nicotine-induced memory impairments, and whether the adverse effects can be
rescued by pharmacological and optogenetic manipulations of α2* nAChR-expressing interneurons. Given
the very limited expression of ...

## Key facts

- **NIH application ID:** 10207576
- **Project number:** 5R01DA041378-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** KATUMI SUMIKAWA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,625
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207576

## Citation

> US National Institutes of Health, RePORTER application 10207576, Maternal nicotine exposure and memory impairments in offspring (5R01DA041378-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10207576. Licensed CC0.

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