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Tytuł pozycji:

Serine Racemase Deletion Affects the Excitatory/Inhibitory Balance of the Hippocampal CA1 Network.

Tytuł:
Serine Racemase Deletion Affects the Excitatory/Inhibitory Balance of the Hippocampal CA1 Network.
Autorzy:
Ploux E; UNICAEN, INSERM, COMETE, Cyceron, CHU Caen, Normandie University, 14000 Caen, France.
Bouet V; UNICAEN, INSERM, COMETE, Cyceron, CHU Caen, Normandie University, 14000 Caen, France.
Radzishevsky I; Department of Biochemistry, Technion-Israel Institute of Technology, Rappaport Faculty of Medicine, Haifa 31096, Israel.
Wolosker H; Department of Biochemistry, Technion-Israel Institute of Technology, Rappaport Faculty of Medicine, Haifa 31096, Israel.
Freret T; UNICAEN, INSERM, COMETE, Cyceron, CHU Caen, Normandie University, 14000 Caen, France.
Billard JM; UNICAEN, INSERM, COMETE, Cyceron, CHU Caen, Normandie University, 14000 Caen, France.
Źródło:
International journal of molecular sciences [Int J Mol Sci] 2020 Dec 11; Vol. 21 (24). Date of Electronic Publication: 2020 Dec 11.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:
CA1 Region, Hippocampal/*metabolism
Racemases and Epimerases/*metabolism
Amino Acids/metabolism ; Animals ; Electrophysiology ; Hippocampus/metabolism ; Long-Term Potentiation/physiology ; Male ; Memory/physiology ; Mice ; Morris Water Maze Test ; Neuronal Plasticity/physiology ; Racemases and Epimerases/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism
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Grant Information:
1480 FONDATION ALZHEIMER
Contributed Indexing:
Keywords: NMDA receptors; d-serine; excitatory/inhibitory balance; hippocampus; memory; synaptic plasticity
Substance Nomenclature:
0 (Amino Acids)
0 (Receptors, N-Methyl-D-Aspartate)
EC 5.1.- (Racemases and Epimerases)
EC 5.1.1.16 (serine racemase)
Entry Date(s):
Date Created: 20201216 Date Completed: 20210315 Latest Revision: 20210315
Update Code:
20240105
PubMed Central ID:
PMC7763099
DOI:
10.3390/ijms21249447
PMID:
33322577
Czasopismo naukowe
d-serine is the major co-agonist of N-methyl-D-aspartate receptors (NMDAR) at CA3/CA1 hippocampal synapses, the activation of which drives long-term potentiation (LTP). The use of mice with targeted deletion of the serine racemase (SR) enzyme has been an important tool to uncover the physiological and pathological roles of D-serine. To date, some uncertainties remain regarding the direction of LTP changes in SR-knockout (SR-KO) mice, possibly reflecting differences in inhibitory GABAergic tone in the experimental paradigms used in the different studies. On the one hand, our extracellular recordings in hippocampal slices show that neither isolated NMDAR synaptic potentials nor LTP were altered in SR-KO mice. This was associated with a compensatory increase in hippocampal levels of glycine, another physiologic NMDAR co-agonist. SR-KO mice displayed no deficits in spatial learning, reference memory and cognitive flexibility. On the other hand, SR-KO mice showed a weaker LTP and a lower increase in NMDAR potentials compared to controls when GABA A receptors were pharmacologically blocked. Our results indicate that depletion of endogenous D-serine caused a reduced inhibitory activity in CA1 hippocampal networks, altering the excitatory/inhibitory balance, which contributes to preserve functional plasticity at synapses and to maintain related cognitive abilities.
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