Transplantation of interneuron precursors into the postnatal cort

Transplantation of interneuron precursors into the postnatal cortex reopens the critical period of ocular

dominance plasticity when transplanted interneurons reach a cellular age equivalent to that of endogenous inhibitory neurons during the normal critical period (Southwell et al., 2010). Recent efforts to derive cortical interneurons from human pluripotent stem cells (hPSCs) or human-induced pluripotent stem cells (hiPSCs) have also emphasized the ability of these cells to differentiation according to an intrinsic program of maturation. Both in vitro and after transplantation into the rodent cortex, human GABAergic interneurons SAR405838 derived from hPSCs or hiPSCs mature following a protracted timeline of several months, thereby mimicking the endogenous human neural development (Maroof et al., 2013 and Nicholas et al., 2013). Altogether, these findings suggest that multiple aspects of the selleck screening library integration of interneurons in cortical networks are regulated by the execution of a maturational

program intrinsic to inhibitory neurons. Several mechanisms dynamically adjust the balance between excitation and inhibition in the adult brain (Haider et al., 2006 and Turrigiano, 2011). However, it is likely that developmental programs are also coordinated to play an important role in this process. Indeed, the relative density of pyramidal cells and interneurons remains relatively constant from early stages of corticogenesis, when both classes of neurons are still migrating to their final destination

(Sahara et al., 2012). One possibility is that the generation of both classes of neurons is coordinated through some kind of feedback mechanism that balances proliferation in the pallium and subpallium. Alternatively, the production of factors controlling many the migration of GABAergic interneurons to the cortex might be proportional to the number of pyramidal cells generated. For example, it has been shown that cortical intermediate progenitor cells (IPCs) produce molecules that are required for the normal migration of interneurons (Tiveron et al., 2006), and mutants with reduced numbers of IPCs have a deficit in cortical interneurons (Sessa et al., 2010). Cell death is another prominent factor regulating neuronal incorporation during development (Katz and Shatz, 1996 and Voyvodic, 1996). It has long been appreciated that a sizable proportion of inhibitory neurons is eliminated from the cerebral cortex through apoptosis during the period of synaptogenesis (Miller, 1995), and recent work estimated that approximately 40% of the interneurons in the cortex perish around this time (Southwell et al., 2012). Similarly, only about half of the adult-born granule cells survive more than a few days after reaching the olfactory bulb (Petreanu and Alvarez-Buylla, 2002). The mechanisms controlling the death of newborn olfactory bulb interneurons have been studied with some detail.

Leave a Reply

Your email address will not be published. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>