Input-specific GABAergic signaling to newborn neurons in adult dentate gyrus.

J Neurosci

Department of Neurobiology and Evelyn McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Published: December 2009

Adult neurogenesis is the multistage process of generating neurons from adult neural stem cells. Accumulating evidence indicates that GABAergic depolarization is an important regulator of this process. Here, we examined GABAergic signaling to newly generated granule cells (GCs) of the adult mouse dentate gyrus. We show that the first synaptic currents in newborn GCs are generated by activation of GABA(A) receptors by GABA with a spatiotemporal profile suggestive of transmitter spillover. However, the GABAergic response is not attributable to spillover from surrounding perisomatic synapses. Rather, our results suggest that slow synaptic responses in newborn GCs are generated by dedicated inputs that produce a relatively low concentration of GABA at postsynaptic receptors, similar to slow IPSCs in mature GCs. This form of synaptic signaling drives robust phasic depolarization of newborn GCs when the interneuron network is synchronously active, revealing a potential mechanism that translates hippocampal activity into regulation of adult neurogenesis via synaptic release of GABA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846629PMC
http://dx.doi.org/10.1523/JNEUROSCI.2727-09.2009DOI Listing

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  • Cholinergic neurons from the diagonal band of Broca (DB) significantly influence adult hippocampal neurogenesis by promoting the growth and development of quiescent radial neural stem cells (rNSCs) in the dentate gyrus (DG).
  • The study shows that the proliferation and morphological changes of rNSCs require the presence of DG granule cells (GCs), indicating their essential role in this cholinergic circuit's function.
  • Single-nucleus RNA sequencing reveals that cholinergic stimulation causes significant transcriptional changes in DG cells, particularly in GCs, highlighting the complex interactions within the neurogenic niche.
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