Prenatal stress enhances excitatory synaptic transmission and impairs long-term potentiation in the frontal cortex of adult offspring rats

Abstract

The effects of prenatal stress procedure were investigated in 3 months old male rats. Prenatally stressed rats showed depressive-like behavior in the forced swim test, including increased immobility, decreased mobility and decreased climbing. In ex vivo frontal cortex slices originating from prenatally stressed animals, the amplitude of extracellular field potentials (FPs) recorded in cortical layer II/III was larger, and the mean amplitude ratio of pharmacologically-isolated NMDA to the AMPA/kainate component of the field potential--smaller than in control preparations. Prenatal stress also resulted in a reduced magnitude of long-term potentiation (LTP). These effects were accompanied by an increase in the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These data demonstrate that stress during pregnancy may lead not only to behavioral disturbances, but also impairs the glutamatergic transmission and long-term synaptic plasticity in the frontal cortex of the adult offspring.

Fig 1. The effects of prenatal stress on immobility (A), mobility (B) and climbing (C) in the forced swim test.

Shown are mean values ± SEM. * p < 0.05. White bars represent control rats (n = 10) and black bars—prenatally stressed rats (n = 10).

Fig 2. Prenatal stress increases the amplitude of the AMPA/kainate component of field potentials (FPs).

Graphs illustrate the effect of prenatal stress on the relationship between stimulus intensity and the mean response amplitude (± SEM) on (A) composite FPs (in normal ACSF), (B) the AMPA/kainate component and (C) the NMDA component of FPs. Black circles—slices (n = 8 to 12) obtained from stressed rats (n = 10), white circles—control slices (n = 8 to 12, obtained from 10 rats). Lines represent fits to the Boltzmann equation (see: Table 1). Insets: examples of representative responses.

Fig 3. Prenatal stress does not modify the intrinsic excitability of layer II/III pyramidal neurons.

(A) Example of a response of a cell from a stressed rat (upper trace) to a depolarizing current pulse (lower trace). (B) Example of an injected current vs. spiking rate relationship in a cell shown in (A). (C) The mean firing threshold (± SEM) and (D) the mean gain (a slope of injected current vs. spiking rate relationship; ± SEM) of pyramidal neurons prepared from control (white bars; 19 cells from 5 rats) and prenatally stressed animals (black bars; 16 cells from 5 rats). The differences are not significant.

Fig 4. Prenatal stress increases the frequency of sEPSCs recorded from layer II/III pyramidal neurons.

(A) Typical examples of raw records from a control neuron (upper trace on the left) and a neuron originating from prenatally stressed rat (lower trace on the left). Traces to the right represent averages of all individual sEPSCs detected during 4 min recordings from a control neuron (upper trace) and a neuron originating from a stressed rat (lower trace). Bar graphs illustrate the effect of prenatal stress on (B) the mean frequency, (C) the mean amplitude, (D) the rise time and (E) the decay time constant of sEPSCs. In B-E, the error bars represent SEM; * p < 0.05. White bars represent neurons (n = 19) originating from control rats (n = 5) and black bars—neurons (n = 16) from prenatally stressed animals (n = 5).

Fig 5. Prenatal stress impairs the induction of LTP.

(A) Plot of the amplitude of FPs (mean ± SEM) recorded in slices obtained from control rats (white circles) and from rats subjected to prenatal stress (black circles). Arrows denote the time of theta-burst stimulation (TBS, repeated 3 times). Insets show superposition of FPs recorded during representative experiments before and after TBS at times indicated by numbers. (B) Mean (± SEM) amplitude of FPs recorded between 60–75 min after TBS in slices prepared from control (n = 10) and prenatally stressed (n = 10) rats. The numbers on the bars indicate the numbers of slices in each group. *** p < 0.001; Mann-Whitney U test.