Phone: (706) 721-0906

Fax:(706) 721-2347

Email: lredmond@mail.mcg.edu

Office: CB-3526

Grant Support as Principal Investigator | Current Projects | Lab | Honors & Awards | Invited Speaker | Selected Publications |

A crucial aspect of cortical development lies in the correct patterning and subsequent maintenance of axonal and dendritic connections. 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. Sensory experience and neuronal activity in the early life of mammals can profoundly influence the patterning and connectivity of neurons. Yet, the molecular mechanisms by which activity controls neuronal structure remain unclear.

Our research is focused on understanding the cellular and molecular mechanisms that regulate neuronal connectivity during the development and differentiation of the mammalian cortex. We are interested in identifying and ascertaining the contribution of activity-driven molecular signals to neuronal development and specifically to dendrite morphology. Understanding the molecular events contributing to neuronal morphology and dendrite development will help us understand how the brain develops and what can go wrong in developmental and neurological disorders.

Our studies have shown that activation of intracellular calcium signaling pathways increases the complexity of dendrites in a transcription dependent manner similar to that reported in learning and memory. Calcium influx induces a dramatic increase in dendrite growth and complexity that is dependent on entry through voltage sensitive calcium channels (VSCCs). Analysis of intracellular calcium activated signaling cascades to identify the molecular signals involved in this morphological response has revealed a positive role in dendrite growth for calcium calmodulin dependent protein kinase IV (CaMK IV), mitogen activated protein kinase (MAPK), and a negative one for CaMK II. A known target of activated MAP kinases and CaM kinases is a protein that has emerged as the prototypical activity-regulated transcription factor, the cAMP response element binding protein (CREB). We have demonstrated that the effects of CaMK IV are mediated through CREB and the CREB transcriptional coactivator, CREB binding protein (CBP). These experiments provide the first evidence that calcium signaling, through activation of CaMK IV, can lead to dramatic dendrite growth.

Additional studies suggest that individual neurons initiate dendrite elaboration in response to activity by differentially altering length, branching and process number. Recently, we have begun exploring the molecular mechanisms by which neurons differentially translate their response to neuronal activity into branching, elongation and addition of processes.

PI: Lori J Redmond, Ph.D.
1 R01 NS046809
Calcium signaling in neuronal differentiation
03/01/04 - 02/28/09

1. ERK signaling mediation of distinct activity-induced morphological changes.
2. In vivo role of calcium signaling in dendrite morphology.

Seungshin Ha: PhD student (2004-present)

Yu-chih Lin: PhD student (2004-present)

Xiaolan Yi: Research Associate

Tharkika Nagendran :Graduate Research Assistant

Kathleen Wallis

• Awarded a NIH National Service Research Award, 1999-2002.
• Graduated summa cum laude from the University of North Carolina at Greensboro, 1987.

Microscopy and Microanalysis Annual Meeting, 2004. Microscopic Analysis of Nervous System Development and Function session.

Ha, S and Redmond, L (2006) ERK signaling is involved in mediating distinct activity-induced morphological changes in cortical neurons. In preparation

Redmond, L and Ghosh, A. (2005) Regulation of dendritic development by calcium signaling. Cell Calcium 37:411-416.

Redmond, L, Kashani, AH and Ghosh, A. (2002) Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription. Neuron 34:999-1010.

Redmond, L and Ghosh, A. (2001) The role of Notch and Rho GTPase signaling in the control of dendritic development. Curr. Op. Neurobiol. 11:111-117.

Redmond, L, Oh, SR, Hicks, C, Weinmaster, G and Ghosh, A. (2000) Nuclear Notch1 signaling and the regulation of dendritic development. Nature Neurosci. 3:30-40.