Adrienne Frostholm, Ph.D

Research Scientist/Adjunct Associate Professor
Department of Pharmacology
5142 Graves Hall
333 W. 10th Avenue
Columbus, OH 43210
Phone: (614) 292-7747
Fax: (614) 292-7232
Email: frostholm.1@osu.edu

Research Interest

Developmental neuropharmacology; chemical neuroanatomy; neuropharmacology of behavior.

The principal focus of my work is to define epigenetic events underlying gamma aminobutyric acidA (GABAA) receptor expression in developming neuronal circuitry. In adult mammals, neuronal inhibition results when GABA binds to pentameric GABAA receptor and opens an inegral chloride channel.  This leads to increased chloride tranpsort and hyperpolarization of the postsynaptic membrane. In contrast, in the neonatal brain, GABA depolarizes the neuronal membrane and acts as a neurotrophic factor. These functional changes are subserved by a switch in receptor subunit composition and occur during a period of major alterations in afferent and efferent synaptic connectivity. Organotypic cultures of the inferior olive are used to examine the role of amino acid neurotransmitters, growth factors, and peptides on subunit switching. In addition, the relative contributions of afferent and efferent contact are evaluated in mutant mice in which the normal timecourse of these events is perturbed. Experimental approaches include in situ hybridization, immunocytochemistry, and receptor autoradiography.  Our experiments suggest that initial expression of GABAA receptor subunits occur independently of synaptic contact with other cells.  Subsequent stabilization and maintenance of these subunits is dependent, however, on synapse-formation and continued-axonal contact with the efferent target.  Although afferent input is not required for GABAA receptor induction, it may influence the level of subunit expression in adult animals.

Additional Projects

1.	Development of ventricular tumors in transgenic mice in which the SV40 T-antigen is driven by the brain-specific FGF-1 promoter.
2.	Genomic organization, expression and function of Type IIB receptor-like protein tyrosine phosphatases in the developing CNS.

Representative Publications

Rotter, A., Rath, S., Evans, J.E. and Frostholm, A., Modulation of gamma aminobutyric acidA (GABAA) receptor subunit transcript levels in olivocerebellar neurons of Purkinje cell degeneration and weaver mutant mice. J. Neurochem. 74:2190-2200, 2000.

Frostholm, A., Evans, J.E. and Rotter, A., Activity-induced changes in GABAA receptor subunit mRNA expression in murine olivocerebellar nuclei. Mol. Brain Res. 85:200-208, 2000.

Chiu, I.-M., Touhalisky, K., Liu, Y., Yates, A. and Frostholm, A., Tumorigenesis in transgenic mice in which the SV40 T-antigen is driven by the brain-specific FGF-1 promoter. Oncogene 19:6229-6239.

Besco, J.A., Frostholm, A., Popesco, M.C., Burghes, A.H.M. and Rotter, A., Genomic organization and alternative splicing of the human and mouse receptor protein tyrosine phosphatase rho (RPTPr) gene. BMC Genomics 2:1, 2001.

Program Affiliations

The Integrated Biomedical Science Graduate Program (http://www.ibgp.org)
Department of Neuroscience http://medicine.osu.edu/neuroscience/index.html