Lisa Beutler

Joined Program: 2006 (from UW Medical Scientist Training Program)
Previous Degree: B.S. Genetics, UC Davis
Palmiter Lab
lbeutler (at) u.washington.edu

Research:
Over the past year I have been working on characterizing a conditional NMDA receptor knockout mouse in Richard Palmiter’s lab. Using a cre-lox system, the lab made a mouse that has the crucial subunit of the NMDA receptor knocked out of all dopamine 1 receptor-expressing cells. This eliminates a major receptor fo r excitatory input from a large number of cells in the brain, many of which are located in the striatum and are important for generating locomotion and promoting locomotor learning.

The mutant mice develop a degenerative locomotor phenotype. Over the past year I have done a longitudinal behavioral study on a cohort of these mice and shown that they become increasingly hypolocomotor as they age. I have begun to look for the cause of the progressive phenotype in these mice. There are no signs of neurodegeneration or gliosis anywhere in the brain, but the symptomatic mice do lack dendritic spines – the location of excitatory synapses – on their striatal medium spiny neurons. I have yet to determine whether younger, asymptomatic knockout mice also lack dendritic spines, or whether they develop spines that degenerate as the mice age. We hope that these mice might help clarify how the NMDA receptor is involved in synaptogenesis in vivo.