The neocortex is involved in execution of cognitive function, and chronic alcohol exposure causes deficits in executive function dependent on the prefrontal cortex (PFC) and these deficits correlate with altered microstructure of the white and grey matter, disruption of glial homeostasis and dysregulated neuroplasticity in the PFC [94–96]. Recent ex vivo studies in the PFC have shown that chronic in vivo alcohol exposure leads to persistent increases in NMDA/AMPA current ratio via NMDARs, enhances LTP and alters glutamatergic neurotransmission [49, 97, 98]. Supporting the findings with in vivo alcohol exposure, studies with superfusion of EtOH in the PFC show that EtOH produces profound alterations in NMDAR mediated excitability of PFC neurons [99, 100]. More notable is that superfusion of EtOH also produces synaptic depression in the PFC and this effect is not modulated in animals that consumed EtOH over months during adulthood [93]. Overall these mechanistic studies have demonstrated that EtOH exposure (both acute and in vivo conditions) dysregulate glutamatergic transmission in the PFC which might contribute to the impairment of learning and memory that is seen in alcohol dependent subjects.
