Back to Search Start Over

Occlusion of activity dependent synaptic plasticity by late hypoxic long term potentiation after neonatal intermittent hypoxia.

Authors :
Goussakov I
Synowiec S
Aksenov DP
Drobyshevsky A
Source :
Experimental neurology [Exp Neurol] 2021 Mar; Vol. 337, pp. 113575. Date of Electronic Publication: 2020 Dec 21.
Publication Year :
2021

Abstract

To elucidate the mechanisms of memory impairment after chronic neonatal intermittent hypoxia (IH), we employed a mice model of severe IH administered at postnatal days 3 to 7. Since prior studies in this model did not demonstrate increased cell death, our primary hypothesis was that IH causes a functional disruption of synaptic plasticity in hippocampal neurons. In vivo recordings of Schaffer collateral stimulation-induced synaptic responses during and after IH in the CA1 region of the hippocampus revealed pathological late phase hypoxic long term potentiation (hLTP) (154%) that lasted more than four hours and could be reversed by depotentiation with low frequency stimulation (LFS), or abolished by NMDA and PKA inhibitors (MK-801 and CMIQ). Furthermore, late phase hLTP partially occluded normal physiological LTP (pLTP) four hours after IH. Early and late hLTP phases were induced by neuronal depolarization and Ca <superscript>2+</superscript> influx, determined with manganese enhanced fMRI, and had increased both AMPA and NMDA - mediated currents. This was consistent with mechanisms of pLTP in neonates and also consistent with mechanisms of ischemic LTP described in vitro with OGD in adults. A decrease of pLTP was also recorded on hippocampal slices obtained 2 days after IH. This decrease was ameliorated by MK-801 injections prior to each IH session and restored by LFS depotentiation. Occlusion of pLTP and the observed decreased proportion of NMDA-only silent synapses after neonatal hLTP may explain long term memory, behavioral deficits and abnormal synaptogenesis and pruning following neonatal IH.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1090-2430
Volume :
337
Database :
MEDLINE
Journal :
Experimental neurology
Publication Type :
Academic Journal
Accession number :
33358869
Full Text :
https://doi.org/10.1016/j.expneurol.2020.113575