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Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats

Spinal cord injury (SCI) results in lasting deficits that include both mobility and a multitude of autonomic-related dysfunctions. Locomotor training (LT) ...

University of Louisville

Rearing in darkness slows the time course of the critical period in visual cortex, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, whereas at 20 weeks dark-reared cats are more plastic [G. D. Mower (1991)Dev. Brain Res., 58, 151-158]. Thus, a stringent criterion is that genes that are important for plasticity in visual cortex will show differences in expression between normal and dark-reared visual cortex that are of opposite direction in young vs. older animals. The present study reports the identification by differential display PCR of Dab-1, the mammalian homolog of the drosophila disabled-1 gene, as a candidate gene for critical period neuronal plasticity, expression of which is regulated according to this criterion in cat visual cortex. Evidence for this bidirectional direction regulation is extended to Dab-1 protein in cat and mouse visual cortex and shown to be specific to visual cortex, not occurring in frontal cortex. The Reelin/Dab-1 pathway has well-documented functions in cell migration during prenatal life and increasing evidence indicates that in postnatal brain the pathway plays a role in synaptic plasticity. The present results extend this evidence by directly implicating Dab-1 in postnatal critical period plasticity of visual cortex.

Identification of disabled-1 as a candidate gene for critical period neuroplasticity in cat and mouse visual cortex.

Rearing in darkness slows the time course of the visual cortical critical period, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, while at 20 weeks dark-reared cats are more plastic [Mower GD (1991) The effect of dark rearing on the time course of the critical period in cat visual cortex. Dev Brain Res 58:151-158]. Thus, genes that are important for visual cortical plasticity should show differences in expression between normal and dark-reared visual cortex that are of opposite direction in young versus older animals. Previously, we showed by differential display polymerase chain reaction and northern blotting that mRNA for Munc13-3, a mammalian homologue of the C. elegans uncoordinated (unc) gene, shows such bidirectional regulation in cat visual cortex [Yang CB, Zheng YT, Li GY, Mower GD (2002) Identification of Munc13-3 as a candidate gene for critical period neuroplasticity in visual cortex. J Neurosci 22:8614-8618]. Here, the analysis is extended to Munc13-3 protein in mouse visual cortex, which will provide the basis for gene manipulation analysis. In mice, Munc13-3 protein was elevated 2.3-fold in dark-reared compared with normal visual cortex at 3.5 weeks and 2.0-fold in normal compared with dark-reared visual cortex at 9.5 weeks. Analysis of variance of protein levels showed a significant interaction, indicating that the effect of dark rearing depended on age. This bidirectional regulation was restricted to visual cortex and did not occur in frontal cortex. Bidirectional regulation was also specific to Munc13-3 and was not found for other Munc13 family members. Munc13 proteins serve a central priming function in synaptic vesicle exocytosis at glutamatergic and GABAergic synapses and this work contributes to the growing evidence indicating a role of Munc13 genes in synaptic plasticity.

Bidirectional regulation of Munc13-3 protein expression by age and dark rearing during the critical period in mouse visual cortex.

In cat visual cortex, critical period neuronal plasticity is minimal until approximately 3 postnatal weeks, peaks at 5 weeks, gradually declines to low levels at 20 weeks, and disappears by 1 year of age. Dark rearing slows the entire time course of this critical period, such that at 5 weeks of age, normal cats are more plastic than dark reared cats, whereas at 20 weeks, dark reared cats are more plastic. Thus, a stringent criterion for identifying genes that are important for plasticity in visual cortex is that they show differences in expression between normal and dark reared that are of opposite direction in young versus older animals.

Identification of α-chimaerin as a candidate gene for critical period neuronal plasticity in cat and mouse visual cortex.

Electrophysiological studies indicate that cat visual cortical critical period neuronal plasticity peaks around 5 weeks and largely disappears by 20 weeks. Dark rearing slows this time course. Normal cats are more plastic than dark-reared cats at 5 weeks, but the opposite is true at 20 weeks. Thus, a stringent criterion for identifying genes controlling neuronal plasticity is that normal and dark rearing produce opposite direction differences in expression between young and older animals. Differential display polymerase chain reaction identified Abelson interacting protein 2 (Abi-2) as a candidate plasticity gene regulated according to this criterion. Western blotting showed bidirectional regulation of Abi-2 protein levels in cats and mice that was specific to visual cortex and did not occur in frontal cortex. Immunohistochemistry indicated developmental changes in Abi-2 laminar expression in cat visual cortex. Dark rearing altered laminar expression such that at 5 weeks, dark-reared cats were similar to 1-week normally reared cats, and at 20 weeks, dark-reared cats were similar to 5-10-week normally reared animals. The effect of dark rearing on both Abi-2 expression levels and laminar expression patterns was to slow the normal developmental process, the same effect seen on physiologically assessed plasticity in visual cortex.

Age and dark rearing bidirectionally regulate the level and laminar pattern of expression of Abelson interacting protein 2 (Abi-2): a novel candidate visual cortical plasticity gene.

Cui Bo Yang

Department of Anatomical Sciences and Neurobiology

University of Louisville

Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats