title: Willed-movement training reduces motor deficits and induces a PICK1-dependent LTD in rats subjected to focal cerebral ischemia.
abstract: 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.
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Central South University, Xiang Ya Road 90, 410008 Changsha, Hunan, China; Department of Rehabilitation, Brain Hospital of Hunan Province, Hunan University of Chinese Medicine, Fu Rong Road 427, Changsha 410007, Hunan, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Tang
authors.forename: Lihong
authors.initials: L
authors.lastname: Tan
authors.forename: Xiaosu
authors.initials: X
authors.lastname: Yang
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Huang
authors.forename: Gaiqing
authors.initials: G
authors.lastname: Wang
authors.forename: Hengheng
authors.initials: H
authors.lastname: Chen
authors.forename: Jingjing
authors.initials: J
authors.lastname: Nie
authors.forename: Simin
authors.initials: S
authors.lastname: Li
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D002219:Carbamates / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D004777:Environment; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009048:Motor Skills / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002219:Carbamates; D002352:Carrier Proteins; D002934:Cinnamates; D003598:Cytoskeletal Proteins; C547580:FSC 231; D009687:Nuclear Proteins; C498298:PICK1 protein, rat
keywords: ACSF; EM; IP; LFS; Long-term depression; MCAO; Motor learning; NC; PI; PICK1; Stroke; Synaptic plasticity; WM; Willed-movement; Willed-movement training; artificial cerebrospinal fluid; environmental modification; fEPSP; field excitatory postsynaptic potential; ischemia penumbra; low-frequency stimulation; middle cerebral artery occlusion; normal control; peri-infarcted