, 1998). Comparison with neocortical development, a region where pioneer neurons E7080 have been extensively described, may be particularly instructive. Indeed, besides their early generation, hippocampal hub cells share several remarkable properties with subsets of subplate neurons including: (1) long distance projections (Chun et al., 1987, Kanold and Luhmann, 2010, Luhmann et al., 2009, Tamamaki and Tomioka, 2010 and Voigt et al., 2001); (2) mature electrophysiological properties

(Hirsch and Luhmann, 2008); (3) the expression of SOM (Chun et al., 1987 and Tamamaki and Tomioka, 2010), and GAD67 (Arias et al., 2002); and (4) a role in driving synchronous activity in immature cortical networks (Dupont et al., 2006, Kanold and Luhmann, 2010 and Voigt et al., 2001) that identifies the subplate as a “hub station” (Kanold and Luhmann, 2010). Whether hub neurons indeed exist in the developing neocortex and persist into adulthood remains an open question. The present finding is also interesting from the perspective of pathology. As alluded to above, these cells may provide robustness against pathological

insults, in particular those resulting from environmental factors influencing brain development. Interestingly, it Ferroptosis tumor was previously shown that the septum-projecting subclass of CA1 SOM-containing neurons is selectively spared in a chronic rat model of Temporal Lobe Epilepsy, indicating that early-born hub neurons may be resistant to epileptogenesis (Cossart et al., 2001). Whether EGins are central to synchronization processes in epileptic networks therefore remains a viable hypothesis, supported by computational simulations (Morgan and Soltesz, 2008). Now that a subpopulation of hub neurons is accessible to of the conditional expression of genes of interest, including optogenetic vectors (Kätzel et al., 2011), the involvement of superconnected neurons in different forms of physiological or pathological oscillations can be explored. All animal use protocols were performed under the guidelines of the French National Ethic Committee for Sciences and Health report on “Ethical

Principles for Animal Experimentation” in agreement with the European Community Directive 86/609/EEC. Double-homozygous Mash1BACCreER/CreER/RCE:LoxP+/+ and Dlx1/2CreER/CreER/RCE:LoxP+/+ ( Batista-Brito et al., 2008 and Miyoshi et al., 2010) male mice were crossed with 7- to 8-week-old wild-type Swiss females (C.E Janvier, France) for offspring production. To induce CreER activity, we administered a tamoxifen solution (Sigma, St. Louis, MO) by gavaging (force-feeding) pregnant mice with a silicon-protected needle (Fine Science Tools, Foster City, CA). We used 2mg of tamoxifen solution per 30 g of body weight prepared at 10 mg/ml in corn oil (Sigma). Pregnant females crossed with Dlx1/2CreER/CreER/RCE:LoxP+/+ males were force-fed at embryonic days 7.5 or 9.