Increased Synaptic Excitation and Abnormal Dendritic Structure of Prefrontal Cortex Layer V Pyramidal Neurons following Prolonged Binge-Like Consumption of Ethanol

Abstract

Long-term alcohol use causes a multitude of neurochemical changes in cortical regions that facilitate the transition to dependence. Therefore, we used a model of long-term, binge-like ethanol consumption in rats to determine the effects on morphology and synaptic physiology of medial prefrontal cortex (mPFC) layer V pyramidal neurons. Following 10 weeks of ethanol consumption, we recorded synaptic currents from mPFC neurons and used neurobiotin filling to analyze their morphology. We then compared these data to measurements obtained from age-matched, water-drinking control rats. We found that long-term ethanol consumption caused a significant increase in total dendrite arbor length of mPFC layer V pyramidal neurons. Dendritic restructuring was primarily observed in basal dendrite arbors, with mPFC neurons from animals engaged in long-term ethanol drinking having significantly larger and more complex basal arbors compared with controls. These changes were accompanied by significantly increased total spine densities and spontaneous postsynaptic excitatory current frequency, suggesting that long-term binge-like ethanol consumption enhances basal excitatory synaptic transmission in mPFC layer V pyramidal neurons. Our results provide insights into the morphological and functional changes in mPFC layer V pyramidal neuronal physiology following prolonged exposure to ethanol and support changes in mPFC activity during the development of alcohol dependence.

Increased Synaptic Strength and mGlu2/3 Receptor Plasticity on Mouse Prefrontal Cortex Intratelencephalic Pyramidal Cells Following Intermittent Access to Ethanol

“…As the present findings indicate that voluntary EtOH differentially affects subtypes of PFC pyramidal cells, we fully expect distinct adaptations across the anatomically and molecularly varied cortical layers. Here, in layer 5, we observed increased synaptic strength in a subset of pyramidal cells, consistent with the modest effect observed by Klenowski and colleagues (2016). We also believe these findings are not inconsistent with the negative results obtained by Cannady and colleagues (2020), considering the effect size, cell type specificity, and additional methodological considerations.…”

Heightened Exploratory Behavior Following Chronic Excessive Ethanol Drinking: Mediation by Neurotensin Receptor Type 2 in the Anterior Paraventricular Thalamus

“…Studies in nondependent excessive drinkers have suggested that alcohol‐induced changes in behavior are linked to changes in the corticolimbic system (Arienzo et al, 2019; Cservenka and Brumback, 2017; de Guglielmo et al, 2016; Hu et al, 2018; Klenowski et al, 2016), with rodent studies establishing this with neurotrophic factors, neurotransmitters, and neuropeptides (Darcq et al, 2015; George et al, 2012; Ketchesin et al, 2016; Lee et al, 2018). Although these studies used drinking models that yielded overall high EtOH consumption, it remains unclear how these neurobiological changes may manifest differently with the higher compared to lower drinking that occurs within a heterogenous population.…”

Size‐Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice

“…B,B′). Representative tracings were taken from NeuroExplorer (MBF Bioscience Inc.) and projected in the xy plane, in a manner similar to past studies (Bandaru et al, ; Klenowski et al, ; Williams et al, ).…”