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Occlusion of activity dependent synaptic plasticity by late hypoxic long term potentiation after neonatal intermittent hypoxia.
- 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.)
- Subjects :
- Animals
Animals, Newborn
CA1 Region, Hippocampal diagnostic imaging
CA1 Region, Hippocampal pathology
Calcium Signaling
Cell Death
Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors
Cyclic AMP-Dependent Protein Kinases metabolism
Electric Stimulation
Excitatory Postsynaptic Potentials
Female
Hypoxia, Brain diagnostic imaging
Hypoxia, Brain pathology
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred C57BL
N-Methylaspartate antagonists & inhibitors
N-Methylaspartate metabolism
Patch-Clamp Techniques
Hypoxia, Brain physiopathology
Long-Term Potentiation
Neuronal Plasticity
Subjects
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