Jay Baraban M.D., Ph.D
Telephone Number: 410-955-2499
Fax Number: 410-614-6249
Johns Hopkins University
School of Medicine
725 North Wolfe St.
Baltimore, MD 21205
Molecular Mechanisms of Neuronal Plasticity
One of the most fascinating questions facing neuroscience is how the nervous system learns. Recent studies indicate that this process involves changes in neuronal morphology and synaptic efficacy. In addition, defects in these processes underlie mental retardation and other neuropsychiatric diseases. Accordingly, we are studying neuronal signaling pathways that mediate these forms of "plasticity". Two specific projects are described below:
The Translin/Trax RNAse complex - Recent studies have implicated microRNA signaling pathways in regulating synaptic signaling and plasticity. Ongoing studies indicate that the translin/trax RNAse complex, which is enriched in neurons, regulates processing of selected microRNAs. Furthermore, translin ko mice display defects in responsiveness to cocaine and in certain forms of synaptic plasticity. Guided by microarray studies conducted on brain tissue from translin ko mice, we have begun to identify microRNAs and transcripts that are dysregulated in these mice and plan to assess their roles in synaptic signaling and plasticity.
Tech: a RhoA GEF - RhoA signaling pathways play a major in regulating neuronal morphology. We have identified an activator of RhoA, called Tech that is highly enriched in brain and selectively expressed in cortical and hippocampal neurons. Overexpression of constitutively active forms of Tech produces dramatic reductions in dendritic arbor complexity. Tech binds to and co-localizes with MUPP1, a synaptic PDZ scaffold protein and is therefore well situated to regulate dendritic morphology. With the recent availability of Tech ko mice generated by our lab, we are poised to study its role in synaptic plasticity.