Long-term alcohol use causes a multitude of neurochemical changes in cortical regions which 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 neurons. Following 10 weeks of ethanol consumption, we recorded synaptic currents from mPFC neurons and used Neurobiotin filling to analyse their morphology. We then compared this 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 neurons. Dendritic restructuring was primarily observed in basal dendrite arbors, with mPFC neurons from long-term ethanol drinking animals having significantly larger and more complex basal arbors compared to controls. These changes were accompanied by significantly increased total spine densities and spontaneous post-synaptic excitatory current frequency, suggesting that long-term binge-like ethanol consumption enhances basal excitatory synaptic transmission in mPFC layer V 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.
Significance Statement: The development of alcohol addiction is a progressive cycle that involves extended periods of heavy alcohol use. Therefore, we investigated the long-term effects of binge-like alcohol consumption on layer V pyramidal neurons in the medial prefrontal cortex (mPFC), a brain region involved in high-order executive processes including impulsivity. We show that the long-term alcohol consumption increases the dendritic arborisation of pyramidal neurons in layer V of the mPFC. These changes were also accompanied by significantly increased spine densities and excitatory synaptic activity in these neurons. Our study also highlights differences between long- and chronic short-term alcohol intake on mPFC structure and function, adding to the importance of implementing long-term drinking models to better understand neuroadaptations facilitating the transition to dependence.
The authors declare no competing financial interests.
Department of Health | National Health and Medical Research Council (NHMRC) ; Australian Research Council (ARC) [FT1110884].