GABA depolarization is required for experience-dependent synapse unsilencing in adult-born neurons
Open accessAbstract
Neural activity enhances adult neurogenesis, enabling experience to influence the construction of new circuits. GABAA receptor-mediated depolarization of newborn neurons in the adult and developing brain promotes glutamatergic synaptic integration since chronic reduction of GABA depolarization impairs morphological maturation and formation of glutamatergic synapses. Here we demonstrate an acute role of GABA depolarization in glutamatergic synaptic integration. Using proopiomelanocortin enhanced-green fluorescent protein reporter mice, we identify a developmental stage when adult-generated neurons have glutamatergic synaptic transmission mediated solely by NMDA receptors (NMDARs), representing the initial silent synapses before AMPA receptor (AMPAR)-mediated functional transmission. We show that pairing synaptic stimulation with postsynaptic depolarization results in synapse unsilencing that requires NMDAR activation. GABA synaptic depolarization enables activation of NMDARs in the absence of AMPAR-mediated transmission and is required for synapse unsilencing induced by synaptic activity in vitro as well as a brief exposure to an enriched environment in vivo. The rapid appearance of AMPAR-mediated EPSCs and the lack of maturational changes show that GABA depolarization acutely allows NMDAR activation required for initial synapse unsilencing. Together, these results also reveal that adult-generated neurons in a critical period for survival use GABA signaling to rapidly initiate functional glutamate-mediated transmission in response to experience.
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For some time after action potential capability emerges, new granule cells exhibit excitatory instead of inhibitory responses to typically inhibitory neurotransmitter GABA, suggesting they are more likely to fire than mature granule cells.
“For some time thereafter, new granule cells exhibit excitatory instead of inhibitory responses to typically inhibitory neurotransmitter GABA (Chancey et al., 2013), suggesting that these cells are more likely to fire than mature granule cells, which are strongly inhibited (Amaral et al., 2007; Pelkey et al., 2017).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Chancey et al., 2013
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- Authors
- Chancey, J. H., Adlaf, E. W., Sapp, M. C., Pugh, P. C., Wadiche, J. I., & Overstreet-Wadiche, L. S.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Wadiche, Jacques I.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-04-10
- Volume
- 33
- Issue
- 15
- Pages
- 6614-6622
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3657840
- OpenAlex
- W2117918613
- Cited by
- 152
- References
- 52
- Citations by year
- 2025: 7 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 13 · 2020: 18 · 2019: 16 · 2018: 10 · 2017: 17 · 2016: 15 · 2015: 22 · 2014: 11 · 2013: 6
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS078887, P30-NS47466, P30NS047466, NS-064025, P30 NS57098, R01NS065920, NS065920, F31NS078887, NS061788, R01NS064025, R56NS064025, P30NS057098, T32NS061788)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD038985, P30 HD38985)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- adult neurogenesis, NMDA receptor, AMPA receptors, silent synapses, experience-dependent synaptic plasticity, environmental enrichment, newborn neurons
- MeSH terms
- Animals, Critical Period, Psychological, Environment, Female, gamma-Aminobutyric Acid, Hippocampus, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Neurons, Pro-Opiomelanocortin, Synapses, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA, Excitatory Postsynaptic Potentials, Mice, Neurogenesis
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