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

By Sean J. Markwardt, Jacques I. Wadiche, Linda Overstreet-Wadiche. 2009

96 citations recorded by the source corpus.

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 GABAA 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Developmental Neuroscience

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Citations in the corpus

New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (2010, background): “However, these immature DGCs receive synaptic GABAergic input, presumably from local interneurons, and the resulting responses have slow rising and decay kinetic”
Visualization and genetic manipulation of adult neurogenesis using transgenic mice (2011, background): “high intracellular Cl concentration (Wadiche et al., 2005; Karten et al., 2006; Markwardt et al., 2009).”
Modification of hippocampal circuitry by adult neurogenesis (2012, background): “, 2006) or marked in transgenic reporter mice (Overstreet et al., 2004; Overstreet-Wadiche et al., 2006; Markwardt and Overstreet-Wadiche, 2008; Markwardt et al., 2009).”
Adult neurogenesis and the plasticity of the dentate gyrus network (2011, background): “occurs during development, early inputs are exclusively GABAergic contacts distributed in the dendrites (Espósito et al., 2005; Overstreet Wadiche et al., 2005; Markwardt et al., 2009).”
Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb (2013, background): “Occasionally, we also observed RABV-traced neurons classified as Ivy/neurogliaform cells, characterized by their compact dendritic tree and dense axonal arborization (29).”