Willed-movement training reduces motor deficits and induces a PICK1-dependent LTD in rats subjected to focal cerebral ischemia.

Willed-movement (WM) training has been implicated in the promotion of motor function in human stroke survivors and focal ischemic rats. However, the molecular basis of changes in synaptic transmission following WM training remains unclear. In addition, studies examining the influence of rehabilitative training, such as skilled motor learning, on long-term depression (LTD) of synapses in the primary motor cortex have produced conflicting results. To identify the possible effects of willed movement on motor recovery, on expression of the protein interacting with C kinase 1 protein (PICK1), and on PICK1 related LTD, littermate rats were randomly divided into four groups: normal control, middle cerebral artery occlusion (MCAO), WM and environmental modification. Neurological and neurobehavioral assessments were performed for the rats with occlusion of the right middle cerebral artery. Double-labeling immunofluorescence staining was performed to detected expression of PICK1 and NeuN. Extracellular recordings were used to detect the basal extracellular field excitatory postsynaptic potentials and LTD with or without PICK1 inhibitor FSC231. The results showed that willed-movement training facilitated motor recovery after MCAO in rats, increased the PICK1 protein levels, and enhanced LTD in the ischemia hemisphere. The enhanced LTD for the rats after willed-movement training was attenuated by FSC231. Our results indicated that willed-movement training can enhance activity-dependent LTD through PICK1-dependent mechanisms in the ischemic hemisphere of rats.