GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

Abstract

SummaryThe 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-toneuroblast glutamatergic signaling to provide strong homeostatic control on the production of adultborn olfactory bulb interneurons.

Medullary neurons in the core white matter of the olfactory bulb: a new cell type

“…The pattern of immunoreactivity directed to GAD and GABA in the RMS has previously been documented (Platel et al 2007). In addition to the numerous differentiating cells immunoreactive with both GAD 65/67 and GABA antisera, scattered MNs somata were also found throughout the bulbar core (Fig.…”

“…Indeed, GABA, an inhibitory neurotransmitter in the adult central nervous system, provokes GABAAreceptor-mediated depolarization in neuronal precursors in the subventricular zone (Wang et al 2003;Farrant and Nusser 2005). Additionally, subventricular zone neuronprogenitors bind anti-GABA antibodies; therefore, GABA is assumed to exert negative feed-back against astrocyte proliferation (Platel et al 2007). One feature relevant for the present study is that GABA influences cell proliferation (LoTurco et al 1995) and promotes cell migration (Behar et al 1996(Behar et al , 1998 and physiological differentiation (Kelsch et al 2009).…”

Neurochemical markers of cells of the periventricular brain area in the masu salmon Oncorhynchus masou (Salmonidae)

“…Long term morphogenetic influence on the differentiation of target neurons and expression of a specific phenotype was shown in studies on mam mals (Ugrumov, 2009;. It was shown that mole cules of neurotransmitters have a significant impact on the development of cells during embryogenesis (Platel et al, 2007), as well as in the course of postembryonic neurogenesis of the subgranular zone of the dentate gyrus of the medial and lower surface of the brain hemisphere (Cameron et al, 1995;Aniol, Stepan (Aniol, Stepanichev, 2007;Platel et al, 2010). The results of our studies allow us to assume that in the diencephalon and medulla oblongata of the masu salmon, TH, GABA, and NADPH d can play the role of signal molecules, which regulate the processes of adult neurogenesis.…”

Proliferation and Differentiation of Neural Stem Cells Are Selectively Regulated by Knockout of Cyclin D1

“…In the adult mammalian brain, the two adult neurogenic regions include the SVZ and the SGZ in the hippocampus, which contain the pool of dividing neural stem cells (Platel et al 2007). SVZ astrocytes have stem cell attributes while radial-type astrocytes are also thought to have stem cell characteristics in the SGZ (Bordey 2006).…”