Chronic Alcohol Exposure Alters Behavioral and Synaptic Plasticity of the Rodent Prefrontal Cortex

In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC

Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol.

BACKGROUND: Exposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder. METHODS: Newborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin striatal neurons were labeled by immunohistochemistry on postnatal day 60. The spatial distribution of parvalbumin interneurons was studied using Voronoi spatial tessellation and their dendritic trees were completely reconstructed. RESULTS: Parvalbumin interneurons of ethanol-treated animals showed a clustered spatial distribution similar to that observed in control animals. The dendritic tree of parvalbumin interneurons was significantly reduced in ethanol-treated animals, as compared with controls. CONCLUSIONS: Striatal parvalbumin interneurons are crucial components of the brain network serving motor control. Therefore, the shrinkage of their dendrites could contribute to the motor and cognitive symptoms observed in fetal alcohol spectrum disorder