Ethanol-induced loss of dendritic spines in accumbens medium spiny neurons. Insights and hints from a computational model.

The nucleus accumbens (Nacc) is a key structure in the neural circuits involved in the control of goal-directed behavior and response to drugs of abuse. Nacc activity is modulated by glutamate- (GLU) and dopamine-(DA) containing projections from cortical and limbic regions respectively, converging on a common postsynaptic target: the medium spiny neuron (MSN). Ethanol (EtOH) withdrawal profoundly changes the physiology and the morphology of MSNs, with a specific pattern of alterations in both dendritic spine and membrane properties. It has been recently proposed that a close relationship exists between EtOH withdrawal-induced reduction of mesolimbic DA activity and the rearrangement of specific dendritic spines in the Nacc shell MSNs. Because of their predictive value, computational models are a powerful tool in neurobiological research. We aimed to test whether experimentally observed EtOH withdrawal-induced effects on MSNs could be reproduced in silico. Further we wanted to model the synaptic triad, a particular synaptic architecture characterized by a reciprocal interaction between DA and GLU afferents, typically found on MSN distal dendrites. We used a Neuron-based biophysically accurate computational model of a Nacc MSN dendrite implementing 3D morphological reconstruction and electrophysiological data. EtOH withdrawal- driven morphological and electrophysiological changes where modeled in order to study the firing rate and discharge pattern of MSNs. The model findings show that changes in the dendritic spine density and the imbalance in DA/GLU input affect the physiological properties of MSN dendrite, possibly altering its plastic properties. Biophysically and morphologically accurate computational models could be used to reproduce and study in silico the alterations observed in Nacc MSN physiology during EtOH withdrawal.