Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior

King, Sarah L, Marks, Michael J, Grady, Sharon R, Caldarone, Barbara J, Koren, Andrei O, Mukhin, Alexey G, Collins, Allan C and Picciotto, Marina R (2003) Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior. Journal of Neuroscience, 23 (9). pp. 3837-3843. ISSN 0270-6474

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Abstract

Prenatal nicotine exposure has been linked to attention deficit hyperactivity disorder and cognitive impairment, but the sites of action for these effects of nicotine are still under investigation. High-affinity nicotinic acetylcholine receptors (nAChRs) contain the .2 subunit and modulate passive avoidance (PA) learning in mice. Using an inducible, tetracycline-regulated transgenic system, we generated lines of mice with expression of high-affinity nicotinic receptors restored in specific neuronal populations. One line of mice shows functional .2 subunit-containing nAChRs localized exclusively in corticothalamic efferents. Functional, presynaptic nAChRs are present in the thalamus of these mice as detected by nicotine-elicited rubidium efflux assays from synaptosomes. Knock-out mice lacking high-affinity nAChRs show elevated baseline PA learning, whereas normal baseline PA behavior is restored in mice with corticothalamic expression of these nAChRs. In contrast, nicotine can enhance PA learning in adult wild-type animals but not in corticothalamic-expressing transgenic mice. When these transgenic mice are treated with doxycycline in adulthood to switch off nAChR expression, baseline PA is maintained even after transgene expression is abolished. These data suggest that high-affinity nAChRs expressed on corticothalamic neurons during development are critical for baseline PA performance and provide a potential neuroanatomical substrate for changes induced by prenatal nicotine exposure leading to long-term behavioral and cognitive deficits.

Item Type: Article
Additional Information: First author
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Q Science > QZ Psychology
Related URLs:
Depositing User: Sarah King - Psychology
Date Deposited: 06 Feb 2012 15:51
Last Modified: 23 Mar 2017 21:32
URI: http://sro.sussex.ac.uk/id/eprint/14776

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