Knocking-down the NMDAR1 subunit in a limited amount of neurons in the rat hippocampus impairs learning

Journal of Neurochemistry
V T CheliD Jerusalinsky

Abstract

Amplicon vectors derived from herpes simplex virus type 1 were built to modify NMDA receptors by expressing antisense RNA for the essential NR1 subunit. Their ability to modify endogenous levels of NR1 was tested in cultures of rat embryo neocortical neurons. We studied behaviour and tested for expression in adult rats injected with those vectors into the dorsal hippocampus to find out which cells and how many appear involved in memory formation. Rats injected with vectors expressing NR1 antisense performed significantly worse than control rats in an inhibitory avoidance task. Immunohistochemistry was performed in brain slices from the same animals. The transduced cells represented 6-7% of pyramidal neurons in CA1, showing that a single gene knockdown of NR1 in a small number of neurons significantly impaired memory formation. Perhaps neurons undergoing synaptic plasticity are more susceptible to NR1 knockdown, and hence NMDAR are particularly required in those neurons undergoing synaptic plasticity during learning, or perhaps, and more likely, there is not a high level of redundancy in the hippocampal circuits involved, leading to the idea that a certain level of NR1 expression/availability appears necessary for memory formati...Continue Reading

References

Nov 7, 1991·Nature·K MoriyoshiS Nakanishi
Jul 1, 1990·Trends in Pharmacological Sciences·G L Collingridge, W Singer
Jan 1, 1994·Annual Review of Neuroscience·M Hollmann, S Heinemann
Jan 7, 1993·Nature·T V Bliss, G L Collingridge
Jan 1, 1996·Brain Research Bulletin·C FrançoisG Percheron
May 14, 1998·Neuroscience and Biobehavioral Reviews·D P Cain
Sep 15, 1999·Nature·Y P TangJ Z Tsien
Aug 6, 2002·Neuron·Andres Barria, Roberto Malinow
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Richard Wing-Chuen WongNobutaka Hirokawa
Jul 30, 2003·Genes, Brain, and Behavior·M F AdroverD Jerusalinsky
Feb 1, 1957·Journal of Neurology, Neurosurgery, and Psychiatry·W B SCOVILLE, B MILNER

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Citations

Jul 13, 2011·Schizophrenia Bulletin·Anouk MarsmanHilleke E Hulshoff Pol
Aug 19, 2014·Journal of Physiology, Paris·Magalí C CercatoDiana A Jerusalinsky
Aug 2, 2007·Expert Opinion on Biological Therapy·Delphine CuchetAlberto L Epstein
Feb 4, 2016·Acta Biochimica Et Biophysica Sinica·Peijun Ju, Donghong Cui
May 14, 2011·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Sanjeev KumarElie J Chidiac
Aug 5, 2009·Neuroscience and Biobehavioral Reviews·Dragos IntaPeter Gass
May 13, 2008·Neuroscience and Biobehavioral Reviews·Vera Bubeníková-ValesováCyril Höschl
Aug 21, 2010·Developmental Medicine and Child Neurology·Ying-Xue DingLi-Ping Zou
Aug 12, 2014·Pharmacology, Biochemistry, and Behavior·Xing LinQuanfang Huang
Oct 9, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Victor BrizCristina Suñol
Sep 7, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Shaoyi ChenBingren R Hu
Sep 6, 2018·Science and Technology of Advanced Materials·Gao YangMan Cheung Ng
Jan 16, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Michelle E SchoberRobert H Lane
Jan 31, 2017·Frontiers in Behavioral Neuroscience·Magali C CercatoMaría V Baez
Aug 17, 2019·Frontiers in Molecular Neuroscience·Gloria Lee, Yi Zhou
Nov 11, 2020·Neuroscience and Biobehavioral Reviews·Salar VaseghiMohammad-Reza Zarrindast

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