Melanie A. Paquette

Postdoctoral Fellow, Behavioral Neuroscience, OHSU
e-mail: paquette@ohsu.edu

Major Areas Neuroplasticity; Loss and recovery of function, especially in response to chemical stress (e.g. neurotoxin-induced Parkinson's Disease) or environmental stress (e.g., Post-Traumatic Stress Disorder).

Education
BA (1995) Brandeis University
MA (1999) Arizona State University
PhD (2005) Arizona State University

Affiliations
International Behavioral Neuroscience
Sigma Xi
Society for Neuroscience
Society for the Teaching of Psychology

Research Interests
My primary focus is neuroplasticity. Specifically, I am interested in loss and recovery of function in response to chemical or environmental stressors. This research involves modeling human disorders in laboratory rats.

For my dissertation, I investigated one mechanism that may underlie early responses to brain damage: enhanced dopamine (DA) synthesis. Specifically, we assessed the biochemical and behavioral changes that follow brain damage induced by two types of lesions: unilateral, intranigral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) to destroy the dopaminergic cell bodies or hemidecortication to remove the cortex. We investigated the effects of DA synthesis inhibition on amphetamine (AMPH)-evoked rotational behavior at 1 or 14 days after damage. Furthermore, to gain insight into the functional implications of early responses to brain damage, we assessed functional abilities at these same times using a sensorimotor test battery. We discovered that AMPH-evoked rotation and locomotion were sensitive to DA synthesis blockade at 14 days post-6-OHDA, but not at 1 day post-6-OHDA or 1 day post-hemidecortication. These data suggest that behavior mediated by the intact hemisphere at 14 days is dependent on DA synthesis, while behavior mediated by the damaged hemisphere at 1 day is independent of synthesis. Furthermore, we observed four diverse profiles of loss and recovery of sensorimotor function: 1) immediate and persistent loss, 2) progressive decomposition, 3) transient loss followed by recovery, and 4) sparing followed by delayed loss. The functional implications of mechanisms underlying early responses to damage (e.g., compensatory or dysfunctional) can be inferred from these profiles.

For my postdoctoral fellowship, I have two aims. First, I am investigating the neurochemical mechanisms underlying L-DOPA induced dyskinesias in the 6-OHDA rat. We hope to delineate pharmacological interventions that will reduce, delay, or prevent the emergence of dyskinesias in response to L-DOPA treatment for Parkinson's Disease. Furthermore, we plan to assess the functional effects of these interventions using behavioral tests. Second, I am interested in assessing the biochemical and behavioral changes observed in Post-Traumatic Stress Disorder (PTSD) with the ultimate goal of developing pharmacological treatments.

Publications
Castañeda, E., Fleming, S., Paquette, M.A., Boat, K., Moffett, J., Stachowiak, E.K., Bloom, D.C., and Stachowiak, M.K. (2005). Assessment of Recovery in the Hemiparkinson Rat: Drug-induced Rotation Is Inadequate. Physiology and Behavior , 84: 525-535.

Manuscripts in Progress
Paquette, M.A., Maher, P.A., Moffett, J., Castañeda, E., Bloom, D.C., and Stachowiak, M.K. Regulation of cell cycle, proliferation, growth, and survival of neural cells by FGF-2 and FGFR1.

Paquette, M.A. and Castañeda, E. Differential sensitivity of amphetamine-induced rotation to dopamine synthesis blockade at 1 and 14 days post-6-OHDA.

Paquette, M.A. and Castañeda, E. Changes in somatosensory and motor capacity after unilateral nigral or cortical damage.