Prenatal choline exposure alters hippocampal responsiveness to cholinergicstimulation in adulthood

Manipulation of dietary choline levels during gestation results in enduring neurobehavioral changes in offspring that last into adulthood. Alterations of hippocampal function and memory are among the most striking changes. De pending upon the measures assessed, prenatal choline supplementation tends to promote excitatory synaptic efficacy in hippocampal circuits while prena tal choline deficiency diminishes it. However, the mechanisms underlying th ese changes remain unclear. Transverse hippocampal slices were prepared fro m adult offspring of dams fed choline supplemented, choline deficient, or c ontrol diets. We assessed paired-pulse inhibition, and excitatory synaptic responsiveness before and after activation of cholinergic receptors with Ca rbachol. Prenatally choline deficient animals yielded significantly fewer e lectrophysiological viable hippocampal slices than did animals from either of the other two treatment groups. Among the slices tested, there were no d ifferences in paired pulse inhibition between the treatment groups. However , transient cholinergic activation resulted in a prolonged enhancement of t he amplitude of the population EPSP (pEPSP) response in slices from prenata lly choline supplemented animals. These results suggest that GABA receptor- mediated inhibition remains intact after prenatal choline manipulations, an d that enhancement of the excitatory responsiveness of hippocampal circuits in slices from prenatally choline supplemented rats may be related in part to an increase in cholinergic tone within the CA1 circuit. (C) 2000 Elsevi er Science B.V. All rights reserved.