Synaptic Inhibition Mediated by Glia

ates a new problem. If the mitogenic signal is also the primary chemoattractive signal toward which these cells migrate, then why should ENS precursors migrate beyond the cecum? One explanation is that as these cells proliferate in the cecum, they compete for the available GDNF and then eventually migrate toward areas of the distal bowel where there are fewer Ret-expressing cells and more free GDNF. While this may be part of the mechanism, these articles suggest that the high level of ET-3 in the cecum also reduces the migration of neural It has become increasingly clear over the past several crest cells toward GDNF sources and allows these cells years that astrocytes can release chemical transmit-to migrate toward another, as yet undefined, trophic ters in response to the activation of neurotransmitter factor. receptors. In this issue of Neuron, Zhang et al. demon-While the manuscripts by Morrison's and Pachnis's strate that the regulated release of one of these glio-research groups each individually provide new insight transmitters, ATP, mediates a form of heterosynap-into the role of endothelin receptor B signaling in ENS tic suppression. development, the contrasting results in these manuscripts demonstrate how complex the cell fate decisions Research over the last decade has changed our view are that allow neural crest cells to populate the bowel. of the integrative capacity of astrocytes, a subtype of The differences in response to GDNF and ET-3 between glial cell. Through groundbreaking work from several NCSC and other early enteric neural crest derivatives laboratories, we now know that these cells are much are particularly striking. The ability of NCSC to proliferate more than " glue " ; they play essential roles in nervous in culture in the absence of Ret (Iwashita et al., 2003) system development and function (Volterra et al., 2002). or EDNRB (Kruger et al., 2003) signaling raises the possi-Some surprising observations have been made during bility that these cells could be used to repopulate the this time. Astrocytes express a plethora of neurotrans-distal aganglionic bowel in patients with Hirschsprung's mitter receptors that can induce calcium signaling, disease. This would then allow autologous transplants which in turn leads to the release of chemical transmit-of NCSC to the distal bowel, eliminating the need for ters. But what are the roles of these gliotransmitters? immunosuppression. The ability of these mutant cells In this issue of Neuron, Zhang et al. (2003) detail their to form mature …