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. We therefore 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. Secondly, CA1 and CA3 neurons from PAE rats are less likely to orthogonalize their firing between directions of travel on a linear track and between contexts 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 context provides a neural systems-level mechanism to explain spatial memory impairment after moderate PAE.