title: Heightened nicotinic regulation of auditory cortex during adolescence.
abstract: 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.
authors: Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California 92697, USA.
authors: Hideki D
authors: HD
authors: Kawai
authors: Ho-An
authors: HA
authors: Kang
authors: Raju
authors: R
authors: Metherate
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000367:Age Factors; D000818:Animals; D001303:Auditory Cortex / Q000187:drug effects / Q000502:physiology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009538:Nicotine / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D011978:Receptors, Nicotinic / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D009538:Nicotine