For instance, PV+ interneurons are absent from layer I (Rymar and Sadikot, 2007), while Martinotti cells are particularly abundant in layers V and VI, and to a minor extent in layers II/III, but nearly absent from layer IV (Ma et al., 2006). In addition, most bipolar or double-bouquet interneurons reside in the supragranular layers of the cortex (Rymar and Sadikot, 2007), while chandelier cells are almost exclusively found in layers II and V in the rodent neocortex (Taniguchi et al., 2013). Navitoclax solubility dmso Even

those interneurons that seem to distribute more or less uniformly through most cortical layers, such as PV+ basket cells, display distinct patterns of connectivity according to their laminar position (Tremblay et al., 2010). This remarkable degree of organization suggests that precise developmental mechanisms control the laminar distribution of cortical interneurons. The laminar distribution of MGE-derived interneurons follows a sequence that is similar to that followed by pyramidal AZD2281 in vivo cells. Thus, early-born MGE-derived interneurons primarily populate the infragranular layers of the neocortex, while late-born interneurons colonize the supragranular layers (Fairén et al., 1986, Miller, 1985, Pla et al., 2006, Rymar and Sadikot, 2007 and Valcanis and Tan, 2003) (Figure 3). This seems to imply that the time of neurogenesis largely determines the laminar allocation of interneurons.

However, several lines of evidence suggest that this is actually not the case. First, CGE-derived interneurons largely concentrate in supragranular layers of the cortex, independently of their birthdate (Miyoshi et al., 2010, Rymar and Sadikot, 2007 and Xu et al., 2004). This indicates that the birthdate is not a universal predictor of laminar

allocation for interneurons. Second, the distribution of MGE-derived interneurons is directly influenced by the position of pyramidal cells (Hevner et al., BRSK2 2004, Lodato et al., 2011 and Pla et al., 2006). For example, the laminar distribution of interneurons is abnormal in reeler mice ( Hevner et al., 2004), and this is not due to the loss of Reelin signaling in interneurons ( Pla et al., 2006) ( Figure 3). These studies led to an alternative hypothesis to explain the laminar distribution of interneurons, according to which interneurons would adopt their laminar position in response to cues provided by specific classes of pyramidal cells. Direct support for this idea derives from experiments in which the laminar position of MGE-derived interneurons was specifically altered by disrupting the laminar distribution of specific classes of pyramidal cells, independently of their birthdate ( Lodato et al., 2011) ( Figure 3). Thus, MGE-derived interneurons appear to occupy deep or superficial layers of the cortex in response to specific signals provided by pyramidal cells located in these layers.