Delayed Development of Adult-Generated Granule Cells in Dentate Gyrus

By Linda Overstreet-Wadiche, AeSoon Bensen, G. Westbrook. 2006

186 citations recorded by the source corpus.

A substantial fraction of adult-generated granule cells in the dentate gyrus survive and integrate into the existing neuronal network. These newborn neurons must navigate the environment of the adult brain, a setting that is presumably less optimized for neuronal maturation compared with that in the developing brain. We used EGFP (enhanced green fluorescent protein) expression in newborn granule cells to compare the maturation of adult-generated granule cells to those generated in neonates. Labeled newborn granule cells had indistinguishable physiological properties in adults and neonates, indicating they were at the same functional stage. However, the maturation of adult-generated granule cells was slower than neonatal-generated granule cells. Depolarizing GABAergic network activity and transcription factor activation were reduced in adults relative to neonates, suggesting a role for neural activity in the maturation of newborn granule cells. Consistent with this idea, maturation was altered in mice lacking the GABA synthetic enzyme GAD65 (glutamic acid decarboxylase 65). Together, these results provide evidence that activity-dependent processes in the local environment influence the maturation of newborn granule cells.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology

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Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “One notable difference is a significantly slower tempo of neuronal maturation in adult compared to embryonic development (Overstreet-Wadiche et al., 2006a; Zhao et al., 2006).”
Hippocampal granule cells opt for early retirement (2010, background): “…paradigm, can be observed to occur from 2 weeks to 5 months (Wang et al., 2000; Snyder et al., 2001; van Praag et al., 2002; Ambrogini et al., 2004; Schmidt-Hieber et al., 2004; Esposito et al., 2005; Ramirez-Amaya, 2005; Song et al., 2005; Ge et al., 2006; Overstreet-Wadiche et al., 2006a,b).”
Brain micro-ecologies: neural stem cell niches in the adult mammalian brain (2008, background): “GABA decreases progenitor proliferation, promotes neuronal differentiation and is critical for the maturation of newly generated neurons (Tozuka et al. 2005; Ge et al. 2006; Overstreet-Wadiche et al. 2006).”
Input-specific GABAergic signaling to newborn neurons in adult dentate gyrus (2009, methodology): “Spontaneous GABAergic synaptic events in newborn GCs are infrequent (Table 1) (Overstreet-Wadiche et al., 2005, 2006; Karten et al., 2006), and evoked PSCs are small in amplitude (26 2 pA; n 24).”
Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. (2007, background): “Interestingly, neuronal activation, such as seizures, accelerates integration of new neurons in the adult hippocampus (Overstreet-Wadiche et al., 2006b).”
GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus (2009, background): “Previous work has identified an important role of GABAergic input (Tozuka et al., 2005; S. Ge et al., 2006; Overstreet-Wadiche et al., 2006) and NMDA-receptor-mediated synaptic input (Tashiro et al., 2006b) on the differentiation, morphological maturation, and integration of young neurons into the…”
Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus (2007, background): “At this stage, immature neurons may receive GABA-mediated excitatory synaptic input”
Integration of New Neurons into Functional Neural Networks (2006, background): “…by physical exercise or other behavioral stimulation administered in previous experiments (van Praag et al., 2002), an issue that is especially relevant given recent evidence that the functional maturation of new neurons in the adult brain is activity dependent (Overstreet-Wadiche et al., 2006b).”
Visualization and genetic manipulation of adult neurogenesis using transgenic mice (2011, background): “Comparison of neonatal and adult eGFP+ newborn granule cells in POMC-eGFP mice also revealed a developmental delay in the adult cells despite similar morphological characteristics (Overstreet-Wadiche et al., 2006a).”
Seizures Accelerate Functional Integration of Adult-Generated Granule Cells (2006, unknown): “Throughout the life span of the mouse, EGFP-labeled newborn cells have similar morphology and exclusively GABAergic synaptic input (Overstreet-Wadiche et al., 2005, 2006).”