CREB controls cortical circuit plasticity and functional recovery after stroke

L Caracciolo; M Marosi; J Mazzitelli; S Latifi; Y Sano; L Galvan; R Kawaguchi; S Holley; M S Levine; G Coppola; C Portera-Cailliau; A J Silva; S T Carmichael

doi:10.1038/s41467-018-04445-9

CREB controls cortical circuit plasticity and functional recovery after stroke

Nat Commun. 2018 Jun 8;9(1):2250. doi: 10.1038/s41467-018-04445-9.

Authors

L Caracciolo¹, M Marosi^{1

2}, J Mazzitelli¹, S Latifi¹, Y Sano^{2

3

4

5

6}, L Galvan⁴, R Kawaguchi^{7

8}, S Holley⁴, M S Levine⁴, G Coppola^{7

8}, C Portera-Cailliau^{1

2}, A J Silva^{2

3

4

5

6}, S T Carmichael^{9

10}

Affiliations

¹ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
² Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
³ Department of Psychology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁴ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁵ Integrative Center for Learning and Memory, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁶ Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁷ Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁸ Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
⁹ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. scarmichael@mednet.ucla.edu.
¹⁰ Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. scarmichael@mednet.ucla.edu.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Mapping
Cyclic AMP Response Element-Binding Protein / genetics
Cyclic AMP Response Element-Binding Protein / metabolism*
Gene Expression Profiling
Male
Mice, Inbred C57BL
Motor Cortex / metabolism
Motor Cortex / physiopathology*
Motor Neurons / metabolism
Motor Neurons / physiology*
Neuronal Plasticity / genetics
Neuronal Plasticity / physiology*
Patch-Clamp Techniques
Recovery of Function / physiology*
Stroke / genetics
Stroke / physiopathology*

Substances

Cyclic AMP Response Element-Binding Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding