Hippocampal Hyperexcitability in Fetal Alcohol Spectrum Disorder: Pathological Sharp Waves and Excitatory/Inhibitory Synaptic Imbalance.

Hippocampal Hyperexcitability in Fetal Alcohol Spectrum Disorder: Pathological Sharp Waves and Excitatory/Inhibitory Synaptic Imbalance. Exp Neurol. 2016 Mar 17; Authors: Krawczyk M, Ramani M, Dian J, Florez CM, Mylvaganam S, Brien J, Reynolds J, Kapur B, Zoidl G, Poulter MO, Carlen PL Abstract Prenatal alcohol exposure (PAE) can lead to long-lasting neurological alterations that may predispose individuals to seizures and neurobehavioral dysfunction. To date, there exists limited information regarding the underlying pathophysiological mechanisms. The hippocampal CA3 region generates excitatory population activity, called sharp waves (SPWs), that provide an ideal model to study perturbations in neuronal excitability at the network and cellular levels. In the present study, we utilized a mouse model of PAE and used dual extracellular and whole-cell patch-clamp recordings from CA3 hippocampal pyramidal cells to evaluate the effect of 1(st) trimester-equivalent ethanol exposure (10% v/v) on SPW activity and excitatory/inhibitory balance. We observed that PAE significantly altered in vitro SPW waveforms, with an increased duration and amplitude, when compared to controls. In addition, PAE slices exhibited reduced pharmacological inhibition by the GABA-A receptor antagonist bicuculline (BMI) on SPW activity, and increased population spike paired-pulse ratios, all indicative of network disinhibition within the PAE hippocampus. Evaluation of...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
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