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Mol Neurobiol. 2020 Jan 8. doi: 10.1007/s12035-019-01854-9. [Epub ahead of print]

Cellular and Molecular Changes in Hippocampal Glutamate Signaling and Alterations in Learning, Attention, and Impulsivity Following Prenatal Nicotine Exposure.

Author information

1
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
2
Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, 92037, USA.
3
Research Laboratory for Stereology and Neuroscience, Bispebjerg Hospital, 2400, Copenhagen, Denmark.
4
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. kak1@sund.ku.dk.

Abstract

Over 70 million European pregnant women are smokers during their child-bearing years. Consumption of tobacco-containing products during pregnancy is associated with several negative behavioral outcomes for the offspring, including a higher susceptibility for the development of attention-deficit/hyperactive disorder (ADHD). In efforts to minimize fetal exposure to tobacco smoke, many women around the world switch to nicotine replacement therapies (NRTs) during the gestational period; however, prenatal nicotine exposure (PNE) in any form has been associated with alterations in cognitive processes, including learning, memory, and attention. These processes are controlled by glutamatergic signaling of hippocampal pyramidal neurons within the CA1 region, suggesting actions of nicotine on glutamatergic transmission in this region if present prenatally. Accordingly, we aimed to investigate hippocampal glutamatergic function following PNE treatment in NMRI mice employing molecular, cellular electrophysiology, and pharmacological approaches, as well as to evaluate cognition in the rodent continuous performance task (rCPT), a recently developed mouse task allowing assessment of learning, attention, and impulsivity. PNE induced increases in the expression levels of mRNA coding for different glutamate receptors and subunits within the hippocampus. Functional alterations in AMPA and NMDA receptors on CA1 pyramidal neurons of PNE mice were suggestive of higher GluA2-lacking and lower GluN2A-containing receptors, respectively. Finally, PNE was associated with reduced learning, attention, and enhanced impulsivity in the rCPT. Alterations in glutamatergic functioning in CA1 neurons parallel changes seen in the spontaneously hypertensive rat ADHD model and likely contribute to the lower cognitive performance in the rCPT.

KEYWORDS:

AMPA receptor; Attention; CA1; Continuous performance task; NMDA receptor; Prenatal nicotine exposure

PMID:
31916029
DOI:
10.1007/s12035-019-01854-9

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