(DBBS Faculty Member)
Anatomy and Neurobiology
Transcriptional Control of Brain Development and Synaptic Plasticity
The ability of the nervous system to adapt and adjust to a changing environment continues throughout the life of an organism. This remarkable feature termed ‘neuronal plasticity’ manifests as both short-term and long-term modifications and is comprised of various structural, physiological and functional alterations. At the cellular level, the molecular mechanisms underlying long-term neuronal plasticity is governed by changes in gene expression brought about by different classes of transcriptional regulators.
My lab is interested in dissecting the functions of one such key transcription factor, Serum Response Factor (SRF) in neuronal plasticity. We have established that SRF is important for activity-dependent plasticity in the mouse hippocampus, a structure important for spatial information processing. However, SRF is dispensable for neuronal survival. Towards identifying and understanding the molecular pathways regulated by SRF, the specific questions being studied are:
1. What are the activity-dependent genes regulated by SRF? For this, we have compared the expression profiles of activity-induced genes in wild type and SRF-ablated neurons in the hippocampus. The functions of several of these candidate genes in modulating synapse function are currently being investigated using a combination of molecular, biochemical and gene knockout studies in mice.
2. What are the SRF associated cofactors in neurons? A biochemical approach is underway to isolate SRF transcriptional complex from neuronal nuclei to identify neuron specific cofactors that are important for SRF function.
3. What are the spatial and temporal requirements of activity-dependent gene expression in the brain during information processing? We are currently ablating SRF in specific cell types within the hippocampal circuitry to dampen the activity-dependent induction of several plasticity genes. This will allow us to dissect the sequence of events during adaptive neuronal plasticity. This will be achieved through molecular, electrophysiological and behavioral assays.
The long term goal of the lab is to deconstruct the signaling pathways and synaptic circuits involved in mammalian learning and memory. Insights from these studies will elucidate how information is integrated by and processed within individual components of the hippocampal neuronal circuitry.
Johnson AW, Crombag HS, Smith DR, Gallagher M and Ramanan N (2010) Effects of serum response factor deletion on conditioned reinforcement. Behavioural Brain Research (Submitted) Full Article >
Donlea JM, Ramanan N, Shaw PJ (2009 Apr 3). Use-dependent plasticity in clock neurons regulates sleep need in Drosophila. Science. 324 (5923): 105-8. Full Article >
Wickramasinghe SR, Alvania RS, Ramanan N, Wood JN, Mandai K, Ginty DD (2008 May 22). Serum response factor mediates NGF-dependent target innervation by embryonic DRG sensory neurons. Neuron. 58 (4): 532-45. Full Article >
Riccio A, Alvania RS, Lonze BE, Ramanan N, Kim T, Huang Y, Dawson TM, Snyder SH, Ginty DD (2006). A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. Mol Cell. 21: 283-94. Full Article >
Ramanan N, Shen Y, Sarsfield S, Lemberger T, Schutz G, Linden DJ, Ginty DD (2005). SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci. 8: 759-67. Full Article >
Chen X, Ye H, Kuruvilla R, Ramanan N, Scangos KW, Zhang C, Johnson NM, England PM, Shokat KM, Ginty DD (2005). A chemical-genetic approach to studying neurotrophin signaling. Neuron. 46: 13-21. Full Article >
Narendrakumar Ramanan, Ph.D.
Office Location: 922 McDonnell
Office Phone: 314-362-0233
Campus Box: 8108