Thus, changes in activity without a change in morphology suggest atypical processing in the NAC likely due to a change in input, possibly from the mPFC. The NAC receives significant glutamatergic projections from layer II/III pyramidal neurons in the mPFC (Jay et al., 1992, Vertes, 2006). Cues predictive of reward elicit mPFC activity and glutamate release in the NAC (Ishikawa et al., 2008, Jodo et al., 2000) with coordinated firing (Moscarello et al., 2007). Further, inhibition of mPFC projection neurons prevents NAC firing and eliminates behavioral responding to cues (Ishikawa et al., 2008). Thus, alterations in mPFC spine density in the ethanol-exposed animals may impair processing and integration of cues (as carried in hippocampal afferents) and this is in turn reflected by impaired activation during motivated behavior in the NAC. A direct test of this hypothesis remains to be done.
