, 2010). A number of studies have focused on the ability of the habenula, particularly the MHb, to oppose the behavioral processes mediated through the VTA (for reviews, see Fowler and Kenny, 2012 and Hikosaka, 2010). The MHb-interpeduncular pathway is cholinergic, and it has been proposed that its effects on VTA neuron firing are mediated indirectly through inhibition of the

PPTg (Maskos, 2008). Decreasing the expression of nAChRs containing the α5 subunit in the MHb results in increased nicotine self-administration (Fowler et al., 2011), suggesting that this cholinergic system normally INCB018424 acts as a brake on drug reward. Taken together, these studies suggest that point-to-point ACh signaling could have opposing behavioral consequences, depending on the receptor subtypes, neuronal populations, and brain areas stimulated, and that effects of ACh mediated through volume transmission could be distinct from those mediated locally. Numerous studies indicate that ACh plays an important role in the regulation of cortical activity over multiple timescales. The precise Imatinib function of ACh on

any given circuit also depends on the specific expression pattern of nAChRs and mAChRs, as well as the temporal dynamics of ACh concentration in the extracellular space. Neocortical ACh function has been linked to control of circuits underlying attention, cue detection, and memory (Hasselmo and Sarter, 2011).

The primary cholinergic input to the cerebral cortex comes from the BF complex including the substantia innominata the nucleus basalis of Meynert (Mesulam, 1995), though Dichloromethane dehalogenase the latter remains debated (Zaborszky et al., 1999). Cholinergic terminals are distributed throughout the cortex, with more dense projections in superficial layers (Mesulam, 1995). The cellular mechanisms underlying the effects of ACh on cortical circuits have been investigated at many levels. Seminal studies revealed that ACh can produce biphasic changes in the activity of pyramidal neurons, the principal excitatory cells in the neocortex, comprising fast inhibition followed by a slow depolarization (McCormick and Prince, 1985, 1986). The fast inhibition is at least partially mediated by the actions of both nAChRs and mAChRs that increase the excitability and firing rates of dendrite-targeting GABAergic interneurons (Arroyo et al., 2012; Couey et al., 2007; Fanselow et al., 2008; Férézou et al., 2002; Gulledge et al., 2007; Kawaguchi and Kubota, 1997).