GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

Abstract

The neurotransmitter GABA exerts a strong negative influence on the production of adult-born olfactory bulb interneurons via tightly regulated, non-synaptic GABAergic signaling. After discussing some findings on GABAergic signaling in the neurogenic subventricular zone (SVZ), we provide data suggesting ambient GABA clearance via two GABA transporter subtypes and further support for a non-vesicular mechanism of GABA release from neuroblasts. While GABA works in cooperation with the neurotransmitter glutamate during embryonic cortical development, the role of glutamate in adult forebrain neurogenesis remains obscure. Only one of the eight metabotropic glutamate receptors (mGluRs), mGluR5, has been reported to tonically increase the number of proliferative SVZ cells in vivo, suggesting a local source of glutamate in the SVZ. We show here that glutamate antibodies strongly label subventricular zone (SVZ) astrocytes, some of which are stem cells. We also show that some SVZ neuroblasts express one of the ionotropic glutamate receptors, AMPA/kainate receptors, earlier than previously thought. Collectively, these findings suggest that neuroblast-to-astrocyte GABAergic signaling may cooperate with astrocyte-to-neuroblast glutamatergic signaling to provide strong homeostatic control on the production of adult-born olfactory bulb interneurons.

Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination

“…Our findings, that BDNF-TrkB signaling is important for adult neurogenesis, is also consistent with previous studies in the developing cerebellum and cortex where BDNF functions in chemotaxis, regulates attachment of neuroblasts to radial glia, and facilitates neuroblast migration from germinal zones to mature structures in a p75-independent process (Behar et al, 1997;Borghesani et al, 2002, Zhou et al, 2007. Previously, the migration of neuroblasts has been shown to depend on neurotransmission among cells, such as the activation of cholinergic synapses existing on migrating precursor cells (Kaneko et al, 2006) or through nonsynaptic GABAergic signaling (Platel et al, 2007). Either the release of BDNF from en passant synapses or endogenously produced BDNF from neuroblasts could serve as the mechanism by which BDNF mediates its effects on OB neurogenesis in an activity dependent manner.…”

Early Formation of GABAergic Synapses Governs the Development of Adult-Born Neurons in the Olfactory Bulb

“…Similarly, GABAergic signaling controls neuroblast migration in the RMS via paracrine effects (Bolteus and Bordey, 2004;Ge et al, 2006;Platel et al, 2008). These early functions demonstrate that GABA spillover might provide important information to neural stem cells and migrating progenitors about the size of the population of neuroblasts already formed (Platel et al, 2007). However, although GABA controls these early developmental stages, the function of GABAergic signaling on the ensuing maturation of GCs has remained elusive.…”

Mesenchymal Stromal Cells and Neural Stem Cells Potential for Neural Repair in Spinal Cord Injury and Human Neurodegenerative Disorders

“…BMP and its receptor that are expressed by the SVZ cells promoting differentiation of the NSCs toward glial phenotype are blocked by Noggin, which is produced by ECs and in contrast drives differentiation into neurons (Lim et al 2000). The most important regulatory neurotransmitters include GABA ( -aminobutyric acid) and glutamate, which maintain homeostasis of newly formed neurons (Platel et al 2007). GABA decreases the proliferation of neuroblasts and NSCs, whereas glutamate stimulates their division.…”