Effects of Ethanol Exposure during Distinct Periods of Brain Development on Hippocampal Synaptic Plasticity

Abstract

Fetal alcohol spectrum disorders occur when a mother drinks during pregnancy and can greatly influence synaptic plasticity and cognition in the offspring. In this study we determined whether there are periods during brain development that are more susceptible to the effects of ethanol exposure on hippocampal synaptic plasticity. In particular, we evaluated how the ability to elicit long-term potentiation (LTP) in the hippocampal dentate gyrus (DG) was affected in young adult rats that were exposed to ethanol during either the 1st, 2nd, or 3rd trimester equivalent. As expected, the effects of ethanol on young adult DG LTP were less severe when exposure was limited to a particular trimester equivalent when compared to exposure throughout gestation. In males, ethanol exposure during the 1st, 2nd or 3rd trimester equivalent did not significantly reduce LTP in the DG. In females, ethanol exposure during either the 1st or 2nd trimester equivalents did not impact LTP in early adulthood, but following exposure during the 3rd trimester equivalent alone, LTP was significantly increased in the female DG. These results further exemplify the disparate effects between the ability to elicit LTP in the male and female brain following perinatal ethanol exposure (PNEE).

Figure 1

The effects of perinatal ethanol exposure (PNEE) during specific trimester equivalents on long-term potentiation (LTP) in the dentate gyrus (DG) of young adult male rats. PNEE during either the 1st (A), 2nd (B), or 3rd (C) trimester equivalents does not result in a significant reduction in DG LTP. (D) Summary of LTP results calculated by assessing the initial phase of the excitatory post-synaptic potentiation (EPSP) slope (10%–80%) at 55–60 min post-theta burst stimulation (TBS). Results are presented as means ± SEM and were considered statistically significant when p < 0.05.

Figure 2

The effects of PNEE during specific trimester equivalents on LTP in the DG of young adult female rats. PNEE during either the 1st (A) or 2nd (B) trimester equivalents does not result in a significant reduction in DG LTP. (C) PNEE during the 3rd trimester equivalent significantly increased LTP in females when compared to their respective ad libitum (p < 0.01) and pair-fed (p < 0.01) controls (see text for additional details on the statistical analysis). (D) Summary of LTP results calculated by assessing the initial phase of the EPSP slope (10%–80%) at 55–60 min post-TBS. Results are presented as means ± SEM and were considered statistically significant when p < 0.05.

Figure 3

Experimental Timeline. On GD1 pregnant dams were assigned to one of seven treatment groups: Ad libitum controls, 1st trimester equivalent ethanol exposure, 1st trimester equivalent pair-fed, 2nd trimester equivalent ethanol exposure, 2nd trimester equivalent pair-fed, 3rd trimester equivalent ethanol exposure, or 3rd trimester equivalent pair-fed (see text for a detailed explanation of the various groups). Blood samples to assess BAC were taken on GD 10 for the 1st trimester equivalent exposure condition, GD20 for the 2nd trimester equivalent exposure condition, and PND 10 for the 3rd trimester equivalent exposure condition. When animals reached experimental age (PNDs 55–70) they were used for in vivo electrophysiological experiments to examine LTP in the DG of the hippocampus. Basal recordings were first obtained by administering a pulse (0.12 ms in duration) at 0.067 Hz (pre-stimulation). Once a stable baseline was observed for at least 15 min, LTP was induced by applying TBS consisting of 10 bursts of 5 pulses at 400 Hz with an inter-burst interval of 200 ms, which was repeated 4 times at 30 s intervals. The pulse duration was changed to 0.25 ms during TBS. Following TBS, baseline stimulation resumed for 60 min (post-stimulation).