CREB controls cortical circuit plasticity and functional recovery after stroke

被引:100
|
作者
Caracciolo, L. [1 ]
Marosi, M. [1 ,2 ]
Mazzitelli, J. [1 ]
Latifi, S. [1 ]
Sano, Y. [2 ,3 ,4 ,5 ,6 ]
Galvan, L. [4 ]
Kawaguchi, R. [7 ,8 ]
Holley, S. [4 ]
Levine, M. S. [4 ]
Coppola, G. [7 ,8 ]
Portera-Cailliau, C. [1 ,2 ]
Silva, A. J. [2 ,3 ,4 ,5 ,6 ]
Carmichael, S. T. [1 ,2 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA
[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA
来源
NATURE COMMUNICATIONS | 2018年 / 9卷
关键词
MEDIATED GENE-EXPRESSION; FOCAL CEREBRAL-ISCHEMIA; EXPERIENCE-DEPENDENT PLASTICITY; DIRECT-CURRENT STIMULATION; MOTOR CORTEX; TONIC INHIBITION; NEURONS; EXCITABILITY; BRAIN; ACTIVATION;
D O I
10.1038/s41467-018-04445-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recovery after stroke, while blocking CREB signaling prevents stroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with the hM4Di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue, demonstrating that by manipulating the activity of CREB-transfected neurons it is possible to turn off and on stroke recovery. CREB transfection enhances remapping of injured somatosensory and motor circuits, and induces the formation of new connections within these circuits. CREB is a central molecular node in the circuit responses after stroke that lead to recovery from motor deficits.
引用
收藏
页数:16
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