, 2013 and Rudy et al., 2011). The expression, function, and regulation of cortical Htr4 receptors

are clearly different. Htr4 receptors are G-protein coupled, and their expression is strongly and specifically increased in corticostriatal pyramidal cells as a result Protease Inhibitor Library cell assay selective serotonin reuptake inhibitor (SSRI) treatment. This has led to the hypothesis that increased Htr4 expression heightens the sensitivity of corticostriatal pyramidal cells to SSRIs, thus improving communication between the cortex and the striatum and contributing to the therapeutic actions of these antidepressants (Schmidt et al., 2012). These two examples of cortical serotonin responses involve different receptors, signaling pathways, cell types, and behavioral outcomes, yet they are elicited by the same neuromodulator. This Selleck Akt inhibitor suggests that any given neuromodulator has the possibility for a wide scope of action. For example, acetylcholine within the cortex has been shown to mediate attention (Froemke et al., 2007) and memory control (Hasselmo, 2006) as well as plasticity (Gil et al., 1997). However, the nucleus basalis is the primary source of acetylcholine to the cortex (Kilgard and Merzenich, 1998), raising the question of

how signaling from a centralized source can mediate such disparate actions. Again, the answer lies in the fact that the receptor families for many modulatory substances are also scattered across distinct cell types and, conversely, that receptors with different signaling capacities

can be coexpressed in the same cell type(s). For instance, both science the neurogliaform and VIP-expressing interneurons express nicotinic acetylcholine (ACH) receptors (Lee et al., 2010) in addition to having Htr3a receptors. Other interneuron classes, such as the Martinotti (Kawaguchi and Shindou, 1998) and basket cells (Kruglikov and Rudy, 2008) as well as pyramidal cells, express muscarinic ACH receptors (McGehee, 2002). Hence, the release of acetylcholine can differentially engage and modulate distinct sets of cortical circuits. For instance, recent studies show that VIP-expressing bipolar cells function in the disinhibition of basket and Martinotti cells in fear association (Letzkus et al., 2011) or motor-sensory gating (Lee et al., 2013), respectively. The ability of these cells to increase their gain in response to ACH may begin to explain how they are effective in associating sensory and motor stimuli to behavioral associations. These are just a few of the myriad of possible recruitment strategies at the brain’s disposal.