Improved Reversal Learning and Working Memory and Enhanced Reactivity to Novelty in Mice with Enhanced GABAergic Innervation in the Dentate Gyrus
Open accessAbstract
The balance between excitation and inhibition controls fundamental aspects of the hippocampal function. Here, we report an increase in the ratio of inhibitory to excitatory neurons in the dentate gyrus, accompanied by γ-aminobutyric acid(A) (GABA(A)) receptor-dependent impairment of synaptic plasticity and enhancement of activity-dependent changes in excitability in anesthetized adult mice deficient for the extracellular matrix glycoprotein tenascin-R (TNR). TNR-deficient mice showed faster reversal learning, improved working memory, and enhanced reactivity to novelty than wild-type littermates. Remarkably, in wild-type and TNR-deficient mice, faster reversal learning rates correlated at the individual animal level with ratios of parvalbumin-positive interneurons to granule cells and densities of parvalbumin-positive terminals on somata of granule cells. Our data demonstrate that modification of the extracellular matrix by ablation of TNR leads to a new structural and functional design of the dentate gyrus, with enhanced GABAergic innervation, that is, enhanced ratio of inhibitory to excitatory cells, and altered plasticity, promoting working memory and reversal learning. In wild-type mice, the enhanced ratio of inhibitory to excitatory cells in the dentate gyrus also positively correlated with reversal learning, indicating that level of inhibition regulates specific aspects of learning independent of the TNR gene.
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Significantly enhanced working memory and reversal learning in the Morris water maze task is found in TNR -/- global knockout mice.
“Similarly, significantly enhanced working memory and reversal learning in the Morris water maze task is found in TNR -/- global knockout mice [113] (Fig. 2C).”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [113]
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- Authors
- Morellini, F., Sivukhina, E., Stoenica, L., Oulianova, E., Bukalo, O., Jakovcevski, I., Dityatev, A., Irintchev, A., & Schachner, M.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Italian Institute of Technology (IT)
- Rutgers, The State University of New Jersey (US)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-03-01
- Volume
- 20
- Issue
- 11
- Pages
- 2712-2727
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2123320547
- Cited by
- 104
- References
- 5
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 3 · 2014: 9 · 2013: 13 · 2012: 9
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- reversal learning, working memory, novelty reactivity, dentate gyrus, GABAergic innervation, tenascin-R, extracellular matrix, parvalbumin interneurons, granule cells, synaptic plasticity, hippocampus, excitation-inhibition balance, GABAA receptor
- MeSH terms
- Animals, Cognition, gamma-Aminobutyric Acid, Interneurons, Learning, Male, Memory, Mice, Inbred C57BL, Neural Inhibition, Mice, Knockout, Dentate Gyrus, Tenascin, Mice
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