Corinna Burger

 

 

Molecular Biology of Learning and Memory Formation and Neurodegenerative Disorders

E-mail: burger@neurology.wisc.edu

Research Strengths: Behavior: Cognition and Emotion, Molecular Neuroscience, Neurobiology of Disease

RESEARCH INTERESTS
The lab is interested in two main problems in molecular neuroscience: the molecular biology of learning and memory, and the genetic mechanisms underlying neurological disorders. The approach we use involves the manipulation of gene expression in a region-specific manner using viral gene delivery.

1. Learning and Memory:
Identification of putative learning and memory genes both in the young and aged rat using Microarrays constitute our starting tools to study the neurobiology of learning and memory going from genes to behavior. Our ultimate goal is to understand the molecular rules that govern memory formation and plasticity in the CNS both early in life and with aging. The first goal in the lab is to screen the genes that were identified in the array experiments at the functional level. Towards that end, we are using recombinant adeno-associated virus (rAAV) as a gene delivery system to overexpress or knock-down function of these candidate genes in the brain in a region-specific manner and examine the resulting phenotypes using well established behavioral tests. Viral gene delivery is a fast way to screen for this long list of genes in a feasible time frame. It takes approximately a couple of months to generate “somatic” transgenic animals from the purification of the virus to expression of the virus in the desired brain region of the animal, to testing the behavior. This technology can also be used to manipulate the expression of one gene or several genes in combination, so the relationships between the different genes in a pathway can be assessed in vivo.

2. Neurodegenerative Disorders:
Our interest in neurodegenerative disorders has been focused on Parkinson’s disease. We want to understand the triggering molecular mechanisms that lead to this devastating disorder. We are trying to define the role of key genes in the maintenance of the dopaminergic phenotype in the substantia nigra. One example is Nurr1, a transcription factor essential for the mesencephalic dopaminergic phenotype. Nurr1 knockout mice die after birth so studying the role of Nurr1 in the adult has been difficult. We have created Nurr1 “somatic” knockouts in the adult rat midbrain using viral delivered ribozymes to investigate the role of Nurr1 in the maintenance of the adult dopaminergic phenotype. We are also focusing on the identification of the unknown target genes that are transcribed by Nurr1. We expect that understanding which genes are regulated by Nurr1 and the effects of down regulation or overexpression of this gene in the adult will help us understand the molecular profile of the dopaminergic neurons that degenerate during Parkinson’s disease.

Lab Website:

http://www.neurology.wisc.edu/burger.html

Selected Publications:

• Burger, C., M.C. Lopez, J.A. Feller, H.V. Baker, N. Muzyczka, and R.J. Mandel. 2007. Changes in transcription within the CA1 field of the hippocampus are associated with age related memory impairments. Neurobiol. Learn. Mem. 87: 21-41. [PDF]
• Eslamboli, A., A. Romero-Ramos, C. Burger, T. Bjorklund, N. Muzyczka, R.J. Mandel, H. Baker, R.M. Ridley, and D. Kirik. 2007. Long-term consequences of human alpha-synuclein over-expression in the primate ventral midbrain. Brain 130: 799-815. [PDF]
• Burger, C., O. Gorbatyuk, M.J. Velardo, W. Williams, C. Peden, I. Williams, S. Zolotukhin, P. Reier, R. Mandel, and N. Muzyczka. 2004. Recombinant AAV viral vectors with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol. Therapy 10: 302-317. [PDF]