Medical Student Research Fellowship for Summer 2012
Mentor: James Bibb
Department: Psychiatry and Neurology and Neurotherapeutics
Room number: NC5.410
Mail Code: 9070
Phone number: 8-4168
Project title: Cell type-specific regulation of neuronal signal transduction
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable):
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
Brief Description of Project:
The limbic system controls mood and is the collective site of memory formation and acquisition. Synaptic plasticity within this circuitry is mediated by signaling networks that integrate neurotransmitter input to adjust neuronal excitability. The striatum serves as the hub of the mesocorticolimbic pathway that mediates reward and motor learning. We have been targeting the function of the neuronal protein kinase Cdk5 in cell-type specific fashion in this region of the brain using D1 and D2 dopamine receptor promoter-driven Cre recombinase mediated conditional gene deletion. We have observed number of provocative behavioral phenotypes in D1 and D2 Cre Cdk5 knockout mice and we are correlating these effects with changes in synaptic plasticity in this brain region. These data are unpublished and a portion of this study that remains is to evaluate the biochemical basis for these changes. This work entails analysis of dopamine and glutamate signaling in lysates of dissected mouse brain regions and possibly in acutely prepared brain slices treated pharmacologically with signaling pathway activators. The student would become adept at quantitative immunoblotting and develop slice pharmacology techniques. The student would need to establish this expertise and then derive data regarding a multitude of signals in which we are interested. This project requires focus and commitment to learning the craft of deriving clear immunoblot data that would integrate with the behavioral and neurophysiological analysis. A number of basic laboratory skills will be needed. Equipping and training a student represents a serious investment and this project is both important and demanding. The student would be expected to not only conduct the experiment, but also analyze the data and present it in figure form along with presentation of the project. The student would be expected to understand the research that they are conducting and be able to discuss it at lab meetings. If the student is successful, and derives publishable data, they may get to be an author on a paper. It is also our hope that the student will enjoy this work and that it will be a positive experience. This is only one of several projects in the lab, to which the student might contribute. The work will be conducted within an environment of excellent and committed scientists and there will be access to many approaches and techniques. In some cases, students may also have the opportunity to contribute to the authorship of a small review or paper and the student would be welcome to present the work in which they were involved at the medical student research symposium.
This research is described in completion in IACUC APN#0958-07-01-1 Signal transduction in the nervous system
Previous Research Activities or Publications with Medical Students:
We have published many papers with medical students, including those in the MSTP program. Here are a few recent examples of papers on which medical students (in bold) doing a summer rotation were authors.
Wang, A. & Bibb, J. A. Is CREB the angry bird that releases memory in Alzheimer's? Neuropharmacology, 36:2153-4, (2011).
Torres-Altoro, M.I., Mathur, B.N., Drerup, J.M., Thomas, R., Lovinger, D., O’Callaghan, J.P., Bibb, J.A. (2011) Orthophosphates dysregulated dopamine signaling, glutamaterigic neurotransmission, and induce neuronal injury markers in striatum, Journal of Neurochemistry. 119:303-13
Barnett, D.G.S. and Bibb, J.A. (2010) The role of Cdk5 signaling in cognition and neuropsychiatric and neurological pathology, Brain Research Bullitin, 85:9-13.