An important role for both nAChRs and mAChRs has been defined in hippocampal synaptic plasticity (reviewed in (Giocomo and Hasselmo, 2007; McKay et al., 2007)) and these effects are mediated through intracellular signaling pathways downstream of mAChRs and nAChRs (reviewed in (Berg and Conroy, 2002; Cancela, 2001; Lanzafame et al., 2003; Rathouz et al., 1996)). Recent studies suggest that the timing of ACh release and the subtype of receptor is critical for the type of plasticity induced (Gu and Yakel, 2011); however, it is clear that nAChRs and mAChRs on both GABAergic and glutamatergic neurons in the hippocampus can alter the subsequent response to excitatory inputs (Drever et al., 2011). Similarly, stimulation of nAChRs on glutamatergic terminals in the VTA can induce long-term potentiation (LTP) of excitatory inputs onto DA neurons (Mansvelder and McGehee, 2000), whereas differential effects of nAChRs on glutamatergic and GABAergic terminals in this area appears to be important for changes in dopaminergic firing following prolonged exposure to nicotine (Mansvelder et al., 2002; Wooltorton et al., 2003).
