Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine
Abstract
Persistent neuronal plasticity, including that observed at some hippocampal synapses, requires N-methyl-D-aspartate (NMDA)-mediated transmission. NMDA receptor activation may be necessary for hippocampus-dependent learning as antagonists block acquisition in many such tasks. The behavioural effects of NMDA agonists are less well defined. We have shown that a monoclonal antibody (B6B21) displaced [3H]-glycine that was bound specifically to the NMDA receptor, and enhanced the opening of its integral cation channel in a glycine-like fashion, effects that were competitively antagonized by 7-chlorokynurenic acid. B6B21 also enhanced long-term potentiation in hippocampal slices. We report here that intraventricular infusions of B6B21 significantly enhances acquisition rates in hippocampus-dependent trace eye blink conditioning in rabbits, halving the number of trials required to reach a criterion of 80% conditioned responses. Peripheral injections of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor which crosses the blood-brain barrier, also doubles rabbits' learning rates. Pseudoconditioning control experiments indicated a lack of nonspecific behavioural sensitization effects. Our data suggest that enhanced activation of the glycine coagonist site on the NMDA receptor/channel complex facilitates one form of associative learning and may be used in other learning tasks.
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Various transgenic and pharmacological approaches that augment NMDAR signaling increase learning and memory in mice.
“Various transgenic and pharmacological approaches that augment NMDAR signaling have been found to increase learning and memory in mice, for example, NR2B overexpression and application of NMDAR partial agonist, D-cycloserine (79,80).”
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- Authors
- Thompson, L. T., Moskal, J. R., & Disterhoft, J. F.
- Affiliations
- Northwestern University (US)
- Venue
- Nature
- Published
- 1992-10
- Volume
- 359
- Issue
- 6396
- Pages
- 638-641
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2033667632
- Cited by
- 182
- References
- 2
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- hippocampus-dependent learning, NMDA receptor, D-cycloserine, long-term potentiation, associative learning, 7-chlorokynurenic acid, intraventricular infusion, blood-brain barrier
- MeSH terms
- Animals, Antibodies, Monoclonal, Conditioning, Eyelid, Cycloserine, Glycine, Hippocampus, Rabbits, Receptors, N-Methyl-D-Aspartate
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