CREB Controls Cortical Circuit Plasticity and Functional Recovery after Stroke

Treatments that stimulate neuronal excitability enhance motor performance after stroke.cAMP-response-element binding protein (CREB) is a transcription factor that plays a key rolein neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool ofmotor neurons enhances motor recovery after stroke, while blocking CREB signaling preventsstroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with thehM4di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue,demonstrating that it is possible to turn off and on stroke recovery by manipulating theactivity of CREB-transfected neurons. CREB transfection enhances re-mapping of injuredsomatosensory and motor circuits, and induces the formation of new connections withinthese circuits. CREB is a central molecular node in the circuit responses after stroke that leadto recovery from motor deficits. Motor cortical neurons in adult C57 mice were transfected with tdTomato or tdTomato-Creb, and received either a stroke or no manipulation (control). 4 weeks after stroke, or 5 weeks after viral injection (control), tdTomato+ neurons were FACS-isolated, total RNA isolated and whole genome microarrays performed. This was done in duplicate. In the sample listing PT = photothrombotic stroke and is the same procedure as stroke.