Control of neuroblast production and migration by converging GABA and glutamate signals in the postnatal forebrain

摘要

The production of adult-born neurons is an ongoing process accounting for > 10 000 immature neurons migrating to the olfactory bulb every day. This high turnover rate necessitates profound control mechanisms converging onto neural stem cells and neuroblasts to achieve adequate adult-born neuron production. Here, we elaborate on a novel epigenetic control of adult neurogenesis via highly coordinated, non-synaptic, intercellular signalling. This communication engages the neurotransmitters GABA and glutamate, whose extracellular concentrations depend on neuroblast number and high affinity uptake systems in stem cells. Previous studies show that neuroblasts release GABA providing a negative feedback control of stem cell proliferation. Recent findings show an unexpected mosaic expression of glutamate receptors leading to calcium elevations in migrating neuroblasts. We speculate that stem cells release glutamate that activates glutamate receptors on migrating neuroblasts providing them with migratory and survival cues. In addition, we propose that the timing of neurotransmitter release and their spatial diffusion will determine the convergent coactivation of neuroblasts and stem cells, and provide a steady-state level of neuroblast production. Upon external impact or injury this signalling may adjust to a new steady-state level, thus providing non-synaptic scaling of neuroblast production.