Cited by 81Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsCellular transport and secretion

Rab3B protein is required for long-term depression of hippocampal inhibitory synapses and for normal reversal learning

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Tsetsenis, Theodoros, Younts, Thomas J., Chiu, Chiayu Q., Kaeser, Pascal S., Castillo, Pablo E., Südhof, Thomas C.·2011·Proceedings of the National Academy of Sciences

Abstract

Rab3B, similar to other Rab3 isoforms, is a synaptic vesicle protein that interacts with the Rab3-interacting molecule (RIM) isoforms RIM1α and RIM2α as effector proteins in a GTP-dependent manner. Previous studies showed that at excitatory synapses, Rab3A and RIM1α are essential for presynaptically expressed long-term potentiation (LTP), whereas at inhibitory synapses RIM1α is required for endocannabinoid-dependent long-term depression (referred to as "i-LTD"). However, it remained unknown whether i-LTD also involves a Rab3 isoform and whether i-LTD, similar to other forms of long-term plasticity, is important for learning and memory. Here we show that Rab3B is highly enriched in inhibitory synapses in the CA1 region of the hippocampus. Using electrophysiological recordings in acute slices, we demonstrate that knockout (KO) of Rab3B does not alter the strength or short-term plasticity of excitatory or inhibitory synapses but does impair i-LTD significantly without changing classical NMDA receptor-dependent LTP. Behaviorally, we found that Rab3B KO mice exhibit no detectable changes in all basic parameters tested, including the initial phase of learning and memory. However, Rab3B KO mice did display a selective enhancement in reversal learning, as measured using Morris water-maze and fear-conditioning assays. Our data support the notion that presynaptic forms of long-term plasticity at excitatory and inhibitory synapses generally are mediated by a common Rab3/RIM-dependent pa…

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Crossref · 10.1073/pnas.1112237108

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  • Deletions of the corresponding Rab3 isoform in a synapse block long-term synaptic plasticity.

    “deletions of the corresponding Rab3 isoform in a synapse appears to also block long-term synaptic plasticity”

    From The Presynaptic Active Zone (2012) · cites this paper as Tsetsenis et al., 2011

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Authors
Tsetsenis, T., Younts, T. J., Chiu, C. Q., Kaeser, P. S., Castillo, P. E., & Südhof, T. C.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Albert Einstein College of Medicine (US)
  • Stanford University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2011-08-15
Volume
108
Issue
34
Pages
14300-14305
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2044824462
Cited by
81
References
57
Citations by year
2026: 1 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 7 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 4
FWCI
3.05
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (MH086403, DA017392)
  • National Institute of Mental Health (P50MH086403)
  • National Institute on Drug Abuse (R01DA017392, K01DA029044)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
Rab3B, long-term depression, inhibitory synapses, hippocampus, CA1, synaptic vesicle proteins, reversal learning, learning and memory, presynaptic plasticity, knockout mice
MeSH terms
Animals, Extinction, Psychological, Fear, Hippocampus, Models, Neurological, Synaptic Transmission, Reversal Learning, Synapses, Gene Deletion, Mice, Knockout, Excitatory Postsynaptic Potentials, rab3 GTP-Binding Proteins, Long-Term Synaptic Depression, Mice, Inhibitory Postsynaptic Potentials, CA1 Region, Hippocampal

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