Monocular Enucleation Induces Nuclear Localization of Calcium/Calmodulin-Dependent Protein Kinase IV in Cortical Interneurons of Adult Monkey Area V1

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Abstract
Elevation of intracellular Ca2+levels activates calcium/calmodulin-dependent protein kinase (CaMK) IV, which in turn plays an important role in neuroprotection and neuroplasticity. The possibility that CaMKIV is similarly involved in neocortical tissue has not been examined previously, especially with regard to the plastic nature of ocular dominance features in the primary visual cortex (area V1). We addressed this question by way of monocular enucleation (ME) to disrupt sensory input and examine CaMKIV expression changes in monkey area V1. Immunohistochemical staining of area V1 in normal infants showed a nuclear presence of CaMKIV, which did not changed after ME. However, a striking set of layer- and time-dependent changes in nuclear CaMKIV expression was observed in adult area V1 after ME. A strong increase in nuclear CaMKIV levels was evident in cortical layers II/III and VI after 1 d of ME and in layer IVC after 5 d of ME. These specific laminar changes persisted after 30 d of ME and, most notably, showed a columnar profile in which CaMKIV expression was linked to open-eye columns. Real-time quantitative reverse transcription-PCR and Western blot analysis showed that total amounts of CaMKIV mRNA and protein remained unchanged after ME, suggesting that a nuclear translocation may occur from the cytoplasm. Finally, double-label immunohistochemical staining with a pyramidal cell marker (SMI-32) showed that CaMKIV was absent in this subtype, whereas coincidental expression with GABA, parvalbumin, and calretinin, but not calbindin, showed its clear presence in a subset of interneurons. We propose that CaMKIV activity within diverse groups of cortical interneurons may play an important role in adaptive plastic reorganization of adult neocortical tissue.