Figure 1.

Schematic illustration of neuronal circuits in the dorsomedial striatum (DMS) and of the effects of acute and chronic ethanol exposure on plasticity in this region. (A) Simplified diagram of the circuits in the DMS, showing glutamatergic cortical inputs to the major projection neurons in the striatum (i.e., medium spiny neurons [MSNs]). Also indicated is GABAergic microcircuitry involving MSN–MSN synapses that tend to innervate dendrites and synapses made by fast-spiking interneurons (FSIs) on MSN cell bodies. These MSNs project out of the striatum to the globus pallidus external segement (GPe) and the substantia nigra pars reticulata (SNr). Boxed areas indicate the predominate sites of synapses on the MSNs. (B) Effects of acute ethanol exposure on plasticity at synapses onto DMS MSNs. The net effects are prevention of normal plasticity (i.e., inhibition of long-term potentiation [LTP]) at excitatory cortical glutamatergic inputs, while a new form of NMDA receptor (NMDAR)-dependent long-term facilitation (LTF) occurs. Increased synaptic inhibition also occurs. Thus, the net signal output from the DMS may be dampened, while responses to associative cortical input may become aberrant. (C) Effects of chronic ethanol exposure on plasticity at synapses in the DMS. Net effects include prolonged LTF and LTP-like increase in AMPA receptor function at glutamatergic synapses, accompanied by net decreases in inhibition. These changes may alter goal-directed ethanol-related behaviors, particularly those controlled by the prefrontal cortex and related associative cortices.