, 1994). Electrophysiological and electron

microscopic studies have also shown extensive local synaptic interactions among basal forebrain neurons (Momiyama and Zaborszky, 2006; Zaborszky and Duque, 2003). This raises the possibility that in addition to the long-range connections between the VLPO and ascending arousal system, sleep-wake switches also depend on the local reciprocal inhibition between the sleep- and wake-active GABAergic neurons and between GABAergic and cholinergic neurons within the basal forebrain/preoptic area (Figure 2, light red and blue arrows). Furthermore, the wake-active neurons in this region may also project to the brainstem and hypothalamus, Selleck Obeticholic Acid DAPT research buy innervating the cholinergic, monoaminergic, as well as glutamatergic or GABAergic neurons (Figure 2, light red arrows). Thus, the flip-flop circuit for sleep-wake switches may involve

multiple loops of excitation and inhibition. Given the large number of GABAergic neurons in the basal forebrain/preoptic area and the importance of GABAergic transmission in sleep-wake regulation (Monti et al., 2010), delineating the functional organization of these neurons may be a key step toward understanding the subcortical circuits controlling brain states. Studies in the neocortex and hippocampus have shown that GABAergic

neurons with distinct molecular markers exhibit different physiological properties and innervation patterns (Ascoli et al., 2008; Fishell and Rudy, 2011), and they play different roles in sensory processing (Lee et al., 2012; Wilson et al., 2012). In the basal forebrain, juxtacellular recordings from a small number of immunocytochemically identified neurons suggest that cells with different sleep-wake activity patterns may also express distinct molecular markers (Duque et al., 2000). Since a large number of Cre driver mouse lines targeting different subtypes of GABAergic neurons have now become available (Taniguchi Rolziracetam et al., 2011), a promising approach is to make a targeted recording from each cell type to determine their sleep-wake activity patterns. Optogenetic manipulation of their activity in a bidirectional manner (Chow et al., 2010; Deisseroth, 2011), which has been achieved in various neuronal circuits, can further establish the causal role of these neurons in brain state regulation (Figure 4). Moreover, recent advances in viral tracing techniques (Wickersham et al., 2007) may greatly facilitate the dissection of synaptic connectivity among the various neuronal subtypes. The thalamus is the gateway of sensory inputs to the cortex, and it receives massive cortical feedback.