Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery that controls the proliferation of tumor cells and perhaps tumor stem cells. Here, we will discuss GABA's presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity.

In the postnatal neurogenic niche, two populations of astrocyte-like cells (B cells) persist, one acting as neural progenitor cells (NPCs, B1 cells) and one forming a structural boundary between the neurogenic niche and the striatum (B2 cells, niche astrocytes). Despite being viewed as two distinct entities, we found that B1 and B2 cells express the gap junction protein connexin 43 and display functional coupling involving 50-60 cells. Using neonatal electroporation to label slowly cycling radial glia-derived B1 cells, which send a basal process onto blood vessels, we further confirmed dye coupling between NPCs. To assess the functionality of the coupling, we used calcium imaging in a preparation preserving the 3-dimensional architecture of the SVZ. Intercellular calcium waves were observed among B cells. These waves travelled bidirectionally between B1 and B2 cells and propagated on blood vessels. Inter-B cell calcium waves were absent in the presence of a gap junction blocker but persisted with purinergic receptor blockers. These findings show that privileged microdomains of communication networks exist among NPCs and niche astrocytes. Such functional coupling between these two cell types suggests that niche astrocytes do not exert a mere structural role, but may play an active role in shaping the behavior of NPCs.

Spatially targeted, genetically-specific strategies for sustained inhibition of nociceptors may help transform pain science and clinical management. Previous optogenetic strategies to inhibit pain have required constant illumination, and chemogenetic approaches in the periphery have not been shown to inhibit pain. Here, we show that the step-function inhibitory channelrhodopsin, SwiChR, can be used to persistently inhibit pain for long periods of time through infrequent transdermally delivered light pulses, reducing required light exposure by >98% and resolving a long-standing limitation in optogenetic inhibition. We demonstrate that the viral expression of the hM4D receptor in small-diameter primary afferent nociceptor enables chemogenetic inhibition of mechanical and thermal nociception thresholds. Finally, we develop optoPAIN, an optogenetic platform to non-invasively assess changes in pain sensitivity, and use this technique to examine pharmacological and chemogenetic inhibition of pain.

Adult neurogenesis occurs in two privileged microenvironments, the hippocampal subgranular zone of the dentate gyrus and the subventricular zone (SVZ) along the lateral ventricle. This review focuses on accumulating evidence suggesting that the activity of specific brain regions or bodily states influences SVZ cell proliferation and neurogenesis. Neuromodulators such as dopamine and serotonin have been shown to have long-range effects through neuronal projections into the SVZ. Local GABA and glutamate signaling have demonstrated effects on SVZ proliferation and neurogenesis, but an extra-niche source of these neurotransmitters remains to be explored and options will be discussed. There is also accumulating evidence that diseases and bodily states such as Alzheimer's disease, seizures, sleep, and pregnancy influence SVZ cell proliferation. With such complex behavior and environmentally-driven factors that control subregion-specific activity, it will become necessary to account for overlapping roles of multiple neurotransmitter systems on neurogenesis when developing cell therapies or drug treatments.

In the postnatal subventricular zone (SVZ), neuroblasts migrate in chains along the lateral ventricle towards the olfactory bulb. AMPA/kainate receptors as well as metabotropic glutamate receptors subtype 5 (mGluR5) are expressed in SVZ cells. However, the cells expressing these receptors and the function of these receptors remain unexplored. We thus examined whether SVZ neuroblasts express mGluR5 and Ca 2+ -permeable kainate receptors in mouse slices. Doublecortin (DCX)-immunopositive cells (i.e. neuroblasts) immunostained positive for mGluR5 and GLU K5−7 -containing kainate receptors. RT-PCR from ∼10 GFP-fluorescent cell aspirates obtained in acute slices from transgenic mice expressing green fluorescent protein (GFP) under the DCX promoter showed mGluR5 and GLU K5 receptor mRNA in SVZ neuroblasts. Patch-clamp data suggest that ∼60% of neuroblasts express functional GLU K5 -containing receptors. Activation of mGluR5 and GLU K5 -containing receptors induced Ca 2+ increases in 50% and 60% of SVZ neuroblasts, respectively, while most neuroblasts displayed GABA A -mediated Ca 2+ responses. To examine the effects of these receptors on the speed of neuroblast migration, we developed a whole-mount preparation of the entire lateral ventricle from postnatal day (P) 20-25 DCX-GFP mice. The GABA A receptor (GABA A R) antagonist bicuculline increased the speed of neuroblast migration by 27%, as previously reported in acute slices. While the mGluR5 antagonist MPEP did not affect the speed of neuroblast migration, the homomeric and heteromeric GLU K5 receptor antagonists, NS3763 and UB302, respectively, increased the migration speed by 38%. These data show that although both GLU K5 receptor and mGluR5 activations increase Ca 2+ in neuroblasts, only GLU K5 receptors tonically reduce the speed of neuroblast migration along the lateral ventricle.