The long term goal of my research program is to understand cellular and molecular mechanisms regulating neuronal development and differentiation, specifically neuronal connectivity. Patterning and connectivity of neurons in vivo is profoundly influenced by neuronal activity. Yet, the molecular mechanisms by which activity controls neuronal structure remain unclear. The overall goals of this research project are to identify and ascertain the contribution of activity-driven molecular signals to neuronal development and specifically to dendrite morphology. We have previously shown that activation of intracellular calcium signaling pathways increases global dendritic complexity in a transcription dependent manner similar to that reported in learning and memory. Activity induced dendritic complexity is mediated by the sequential activation of CaM kinase IV and CREB/CBP-mediated signaling.
The specific aims of this project are: (i) to determine the mechanisms by which activity is transduced into dendritic branching and process initiation, (ii) to ascertain the requirement for CaMKIV- and CREB-mediated signaling in dendritic development and gene transcriptional control of dendritic elaboration, and (iii) to ascertain in vivo dendrite development in the absence of CaMKIV or CREB signaling. Failure to develop normal neuronal morphology and establish appropriate connections within the central nervous system is believed to be a central feature of mental retardation. Understanding the molecular events contributing to neuronal morphology and dendrite development will help us understand how the brain develops, what can go wrong in developmental disorders, and identify potential targets for therapeutic intervention.
| Nagendran, T; Hardy, L R (2011) Calcium/calmodulin-dependent protein kinase IV mediates distinct features of basal and activity-dependent dendrite complexity. Neuroscience 199:548-62 |
| Ha, Seungshin; Redmond, Lori (2008) ERK mediates activity dependent neuronal complexity via sustained activity and CREB-mediated signaling. Dev Neurobiol 68:1565-79 |
