Calcium/calmodulin-dependent protein kinase IV mediates distinct features of basal and activity-dependent dendrite...

Intracellular signaling mechanisms translate extracellular signals, such as neuronal activity, into effects on dendrite complexity. Deciphering these mechanisms has considerable impact on understanding how the brain develops and what can go wrong in developmental disorders. How neurons regulate intracellular signaling to control their dendrite morphology remains poorly understood and is likely to be determined at the level of individual neuronal types. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a signaling mechanism involved in the regulation of gene expression and dendrite growth. Expression of CaMKIV is developmentally regulated in the cerebral cortex, with highest expression occurring concomitant with the period of extensive dendrite growth and elaboration. Interestingly, cortical neurons heterogeneously expressed CaMKIV in postnatal rat cortices and cortical neurons in vitro. We tested if this differential CaMKIV expression mediated distinct arborization patterns in the dendrites of pyramidal and non-pyramidal neurons. In fact, CaMKIV mediated dendrite complexity via regulation of specific morphological features of the dendrite arbor: branching and elongation, but not primary dendrite formation. We found that small interfering RNA (siRNA) knockdown of CaMKIV decreased basal dendrite complexity indicating that endogenously expressed CaMKIV mediated dendrite complexity. CaMKIV was also required for activity-induced dendrite elaboration. Active CaMKIV expression in cortical neurons increased dendrite elaboration indicating that enzymatic activity was involved. These data indicated neuronal CaMKIV expression was required for basal and activity-induced dendrite complexity. Further, the data presented in this study indicate CaMKIV contributes to the diversity of dendrite arbors via restricted expression and regulation of distinct modes of dendrite elaboration.