Impaired Peri-infarct Long-Term Potentiation Suggests Alternative Mechanisms of Post-stroke Recovery in Rats
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Background
Early after stroke, a period of heightened plasticity in the peri-infarct cortex is thought to provide the physiological substrate for functional motor recovery through increased expression of long-term potentiation (LTP). Prior slice electrophysiology studies on the capacity for LTP after stroke reported conflicting results. Slice preparation could have influenced the results by disrupting neuromodulatory processes altered after stroke. Therefore, whether LTP can be induced in the peri-infarct cortex remains to be elucidated. We investigated LTP in the peri-infarct cortex of anesthetized rats using a novel in vivo method that preserves local and long-range circuit dynamics.
Methods
LTP, synaptic transmission and short-term plasticity were assessed under urethane anaesthesia in 15 rats (11 with focal stroke to the primary motor cortex, and 4 sham operated controls). Rats were tested one or two weeks after stroke using a minimally perturbed in vivo LTP induction protocol validated in naïve rats. Motor function was evaluated using the cylinder test at baseline and at one or two-weeks post stroke.
Results
LTP in the peri-infarct cortex was supressed in the stroke group compared to sham controls. In addition, synaptic transmission was reduced for higher stimulation intensities, and short-term plasticity shifted from facilitation to depression, indicating impaired synaptic function at one- and two-weeks post-stroke. Behaviorally, the lesioned rats exhibited motor deficits at one week but showed full recovery by two weeks post-stroke.
Conclusion
In recovering animals, both LTP and synaptic transmission are profoundly impaired in the peri-infarct cortex. These findings suggest that mechanisms other than LTP-based plasticity underlie motor recovery during this stage.
