Impaired peri-infarct long-term potentiation in anaesthetized rats suggests alternative mechanisms of post-stroke recovery.

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). Previous slice electrophysiology studies on the capacity for LTP after stroke reported conflicting results. Slice preparation could have influenced the results by disrupting neuromodulatory processes known to be altered after stroke. Therefore, whether LTP can be induced in the peri-infarct cortex remains to be elucidated. In this study, we assessed synaptic transmission, short-term plasticity and LTP, operationalized as increased evoked field potentials, in 15 rats under urethane anaesthesia (11 with focal stroke to the primary motor cortex, and four 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. The results showed a strong reduction of the capacity for LTP in the M1 peri-infarct cortex in comparison with the sham rats. 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. Behaviourally, the lesioned rats exhibited motor deficits at one week but showed full recovery two weeks post-stroke. The results suggest that both LTP and synaptic transmission are profoundly impaired in the peri-infarct cortex during motor recovery after a stroke in M1. KEY POINTS: Increased expression of LTP in the peri-infarct cortex is thought to support motor recovery after stroke. However, to what extent LTP can be induced in the peri-infarct cortex remains unclear. We investigated whether, and to what extent, LTP can be induced in the peri-infarct cortex after an ischaemic stroke in urethane-anaesthetized rats using a novel stimulation protocol developed in naïve rats. The results show that LTP can be induced in the primary motor cortex (M1) in naïve and sham-operated rats by simultaneously stimulating the ventral tegmental area and M1. One and two weeks after a focal ischaemic stroke, the capacity for LTP induced using this method was strongly reduced in the peri-infarct cortex in recovering rats. Our results suggest that spontaneous recovery is independent of the capacity for LTP in the peri-infarct M1.