Electrophysiological correlates of neural plasticity compensating for ischemia-induced damage in the hippocampus.
Injury to the brain often results in loss of synapses or cell death in the damaged area. Subsequent to the injury, the areas that are not directly affected often exhibit enhanced neuronal plasticity. Although there are many reports of morphological changes resulting from such plasticity, their functional consequences are poorly understood. In this study we examined electrophysiological changes associated with ischemia-induced neurogenesis in the hippocampus, a brain region that is particularly vulnerable but also exceptionally plastic. Transient global ischemia was induced in Sprague-Dawley rats by occlusion of both carotid arteries and a reduction in blood pressure for 12 min. The procedure resulted in delayed cell death in the CA1 field of the hippocampus while the dentate gyrus (DG) was spared. To assess neurogenesis and synaptic changes in parallel we used both hemispheres from each animal. One side was used for immunohistochemistry and the other for in vitro electrophysiological experiments in brain slices. Synaptic field responses and synaptic plasticity (LTP) in perforant path within the DG were reduced by 50% at 10 days after the ischemic injury but recovered at 35 days. Synaptic responses in non-neurogenic CA1 were abolished in parallel with cell death and did not recover. Gamma irradiation applied focally to the head selectively prevented neurogenesis and the synaptic recovery in the DG. These experiments reveal electrophysiological changes associated with reactive neural plasticity in the hippocampus.
Wang
Sabrina
S
Department of Physiology, University of Toronto, 1 King's College Circle, Medical Sciences Building, Toronto, ON, M5S 1A8, Canada.
Kee
Nohjin
N
Preston
Edward
E
Wojtowicz
J Martin
JM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000502:physiology / Q000528:radiation effects; D002544:Cerebral Infarction / Q000503:physiopathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D009410:Nerve Degeneration / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D019580:Perforant Pathway / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology / Q000528:radiation effects; D009435:Synaptic Transmission / Q000502:physiology / Q000528:radiation effects
D015415:Biomarkers; D001973:Bromodeoxyuridine