Heightened Nicotinic Regulation of Auditory Cortex during Adolescence
Open accessAbstract
Adolescent smoking is associated with auditory-cognitive deficits and structural alterations to auditory thalamocortical systems, suggesting that higher auditory function is vulnerable to nicotine exposure during adolescence. Although nicotinic acetylcholine receptors (nAChRs) regulate thalamocortical processing in adults, it is not known whether they regulate processing at earlier ages since their expression pattern changes throughout postnatal development. Here we investigate nicotinic regulation of tone-evoked current source density (CSD) profiles in mouse primary auditory cortex from just after hearing onset until adulthood. At the youngest ages, systemic nicotine did not affect CSD profiles. However, beginning in early adolescence nicotine enhanced characteristic frequency (CF)-evoked responses in layers 2–4 by enhancing thalamocortical, early intracortical, and late intracortical response components. Nicotinic responsiveness developed rapidly and peaked over the course of adolescence, then declined thereafter. Generally, responsiveness in females developed more quickly, peaked earlier, and declined more abruptly and fully than in males. In contrast to the enhancement of CF-evoked responses, nicotine suppressed shorter-latency intracortical responses to spectrally distant (non-CF) stimuli while enhancing longer-latency responses. Intracortical infusion of nAChR antagonists showed that enhancement of CF-evoked intracortical processing involves α4β2*, but not α7, nAChRs, whereas both receptor subtypes regulate non-CF-evoked late intracortical responses. Notably, antagonist effects in females implied regulation by endogenous acetylcholine. Thus, nicotinic regulation of cortical processing varies with age and sex, with peak effects during adolescence that may contribute to the vulnerability of adolescents to smoking.
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Sex differences in nicotine sensitivity at different phases of adolescence have been reported in preclinical studies.
“Sex differences in nicotine sensitivity at different phases of adolescence have also been reported in preclinical studies (Cao et al. 2010; Kawai et al. 2011; Lenoir et al. 2015), and are consistent with clinical observations of differing developmental trajectories of tobacco use in males and females (Chen & Jacobsen, 2012).”
From <scp>N</scp> icotine and the adolescent brain (2015) · cites this paper as Kawai et al. 2011
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Self-citation
- Authors
- Kawai, H. D., Kang, H.-A., & Metherate, R.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Metherate, Raju
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-10-05
- Volume
- 31
- Issue
- 40
- Pages
- 14367-14377
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3210642
- OpenAlex
- W2042210599
- Cited by
- 25
- References
- 70
- Citations by year
- 2026: 2 · 2024: 1 · 2022: 1 · 2021: 2 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 3 · 2013: 4 · 2012: 2
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (R01DA012929, R01 DA12929)
- National Institute on Deafness and Other Communication Disorders (P30 DC08369, P30DC008369, R03DC08204, R03DC008204, R01 DC-02967, R01DC002967)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroscience and Music Perception
- Keywords
- nicotine, nicotinic acetylcholine receptors, primary auditory cortex, adolescence, current source density, sex differences, alpha4beta2 nAChR, alpha7 nAChR, endogenous acetylcholine, adolescent smoking, auditory development
- MeSH terms
- Acoustic Stimulation, Age Factors, Animals, Auditory Cortex, Evoked Potentials, Auditory, Female, Injections, Intraventricular, Male, Nicotine, Receptors, Nicotinic, Nicotinic Antagonists, Mice, alpha7 Nicotinic Acetylcholine Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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