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Altered Hippocampal Place Cell Representation and Theta Rhythmicity following Moderate Prenatal Alcohol Exposure.

ABSTRACT: Prenatal alcohol exposure (PAE) leads to profound deficits in spatial memory and synaptic and cellular alterations to the hippocampus that last into adulthood. Neurons in the hippocampus called place cells discharge as an animal enters specific places in an environment, establish distinct ensemble codes for familiar and novel places, and are modulated by local theta rhythms. Spatial memory is thought to critically depend on the integrity of hippocampal place cell firing. Therefore, we tested the hypothesis that hippocampal place cell firing is impaired after PAE by performing in vivo recordings from the hippocampi (CA1 and CA3) of moderate PAE and control adult rats. Our results show that hippocampal CA3 neurons from PAE rats have reduced spatial tuning. Second, CA1 and CA3 neurons from PAE rats are less likely to orthogonalize their firing between directions of travel on a linear track and between changes in contextual stimuli in an open arena compared to control neurons. Lastly, reductions in the number of hippocampal place cells exhibiting significant theta rhythmicity and phase precession were observed, which may suggest changes to hippocampal microcircuit function. Together, the reduced spatial tuning and sensitivity to contextual changes provide a neural systems-level mechanism to explain spatial memory impairment after moderate PAE.

SUBMITTER: Harvey RE

PROVIDER: S-EPMC7511441 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsTo test whether non-dependent drinkers show place preference for a location paired with alcohol, and to test if the amount of time spent in the alcohol-paired location is related to self-reported subjective alcohol effects experienced in that environment.DesignTwo groups of subjects completed six conditioning sessions: three with alcohol (0.8 g/kg) and three without alcohol. Individuals were assigned randomly to two groups, paired and unpaired, in a 2 : 1 ratio. The paired group (n = 78) received alcohol in one testing room and no-alcohol in another testing room (biased assignment). The unpaired group (n = 30) received alcohol and no-alcohol in each testing room.SettingHuman Behavioral Pharmacology Laboratory, University of Chicago, Chicago, IL, USA (single site).ParticipantsHealthy male and female social drinkers (n = 108) aged 21-40 years participated in the study (consisting of 10 separate laboratory visits) between March 2012 and August 2014 (an average of 36 separate subject visits per month).MeasurementsThe primary outcome measure was the pre- to post-conditioning change in the percentage of time spent in the least preferred room (obtained during drug-free exploration tests conducted at separate visits before and after the six conditioning sessions were completed). Secondary measures included self-reported subjective mood and drug effects obtained during the conditioning sessions.FindingsThe groups differed in the change in the percentage of time spent in the initially least preferred room, from pre- to post-conditioning; paired group = 11.0%, unpaired group = -1.4%, mean difference = 12.4%, 95% confidence interval = 1.9-23.0, P = 0.02. The change in the percentage of time spent in the least-preferred room was related to the self-reported sedative effects of alcohol during conditioning sessions among paired group participants only.ConclusionsNon-dependent consumers of alcohol appear to develop a behavioral preference for locations paired with alcohol consumption, more so for those who experience sedative effects from alcohol in those locations.

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Altered Hippocampal Place Cell Representation and Theta Rhythmicity following Moderate Prenatal Alcohol Exposure.

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