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The Journal of Neuroscience, June 25, 2008, 28(26):6592-6606; doi:10.1523/JNEUROSCI.0622-08.2008

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Development/Plasticity/Repair
In Vivo Calcium Imaging Reveals Functional Rewiring of Single Somatosensory Neurons after Stroke

Ian R. Winship^1,2 and Timothy H. Murphy¹

¹Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3, and ²Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2G3

Correspondence should be addressed to Dr. Timothy H. Murphy, Department of Psychiatry, Brain Research Centre, 4N1-2255 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Email: thmurphy{at}interchange.ubc.ca

Functional mapping and microstimulation studies suggest that recovery after stroke damage can be attributed to surviving brain regions taking on the functional roles of lost tissues. Although this model is well supported by data, it is not clear how activity in single neurons is altered in relation to cortical functional maps. It is conceivable that individual surviving neurons could adopt new roles at the expense of their usual function. Alternatively, neurons that contribute to recovery may take on multiple functions and exhibit a wider repertoire of neuronal processing. In vivo two-photon calcium imaging was used in adult mice within reorganized forelimb and hindlimb somatosensory functional maps to determine how the response properties of individual neurons and glia were altered during recovery from ischemic damage over a period of 2–8 weeks. Single-cell calcium imaging revealed that the limb selectivity of individual neurons was altered during recovery from ischemia, such that neurons normally selective for a single contralateral limb processed information from multiple limbs. Altered limb selectivity was most prominent in border regions between stroke-altered forelimb and hindlimb macroscopic map representations, and peaked 1 month after the targeted insult. Two months after stroke, individual neurons near the center of reorganized functional areas became more selective for a preferred limb. These previously unreported forms of plasticity indicate that in adult animals, seemingly hardwired cortical neurons first adopt wider functional roles as they develop strategies to compensate for loss of specific sensory modalities after forms of brain damage such as stroke.

Key words: stroke; ischemia; two-photon; calcium; intrinsic optical signals; forelimb; hindlimb; plasticity; functional imaging; remapping

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Received Feb. 11, 2008; revised April 24, 2008; accepted May 22, 2008.

Correspondence should be addressed to Dr. Timothy H. Murphy, Department of Psychiatry, Brain Research Centre, 4N1-2255 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Email: thmurphy{at}interchange.ubc.ca

This article has been cited by other articles:

				I. R. Winship and T. H. Murphy Remapping the Somatosensory Cortex after Stroke: Insight from Imaging the Synapse to Network Neuroscientist, October 1, 2009; 15(5): 507 - 524. [Abstract] [PDF]

				A. Sigler, M. H. Mohajerani, and T. H. Murphy Imaging rapid redistribution of sensory-evoked depolarization through existing cortical pathways after targeted stroke in mice PNAS, July 14, 2009; 106(28): 11759 - 11764. [Abstract] [Full Text] [PDF]

				C. E. Brown, K. Aminoltejari, H. Erb, I. R. Winship, and T. H. Murphy In Vivo Voltage-Sensitive Dye Imaging in Adult Mice Reveals That Somatosensory Maps Lost to Stroke Are Replaced over Weeks by New Structural and Functional Circuits with Prolonged Modes of Activation within Both the Peri-Infarct Zone and Distant Sites J. Neurosci., February 11, 2009; 29(6): 1719 - 1734. [Abstract] [Full Text] [PDF]

				R. W Li, S. A Klein, and D. M Levi Prolonged Perceptual Learning of Positional Acuity in Adult Amblyopia: Perceptual Template Retuning Dynamics J. Neurosci., December 24, 2008; 28(52): 14223 - 14229. [Abstract] [Full Text] [PDF]

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