Unilateral hippocampal ablation at birth causes a reduction in contralateral LTP.
Subcortical damage in neonates often has more severe consequences than in adults. Unilateral electrolytic hippocampal lesions in adult rats typically result in transient memory deficits, whereas neonatal lesions cause lasting memory impairments. We hypothesized that unilateral lesions made at birth may affect synaptic physiology in the contralateral hippocampus. Consequently, the ability to sustain long-term potentiation (LTP), a form of synaptic plasticity believed to underlie certain forms of memory, was compared between slices from the remaining hippocampus of rats lesioned as newborns and as adults. Initial studies showed that a train of 10 stimulation bursts patterned after the hippocampal theta rhythm produced robust and stable LTP both in slices from controls and rats lesioned at birth. However, a theta burst pattern of stimulation closer to intrinsic physiology (five burst pairs separated by 30 s each), induced significantly less LTP in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults. To investigate possible mechanisms underlying the deficit, the degree of paired-pulse facilitation (PPF) as well as the amount of depolarization occurring between two successive theta bursts were analyzed. The lesion did not detectably change PPF characteristics, suggesting that presynaptic mechanisms are normal. However, the extent to which a burst response was increased by a prior burst was significantly diminished in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults, indicating that postsynaptic factors involved in the initial triggering events of LTP are affected by the lesion. Reduced ability to sustain LTP in the remaining hippocampus may contribute to impaired memory function after unilateral neonatal hippocampal lesion.
van Praag
H
H
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJ, Piscataway, NJ 08854, USA. vanpraag@salk.edu
Chun
D
D
Black
I B
IB
Stäubli
U V
UV
D000818:Animals; D000831:Animals, Newborn; D003714:Denervation; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology* / Q000601:surgery*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013826:Theta Rhythm