PT  - JOURNAL ARTICLE
AU  - Genevieve A. Laforet
AU  - Ellen Sapp
AU  - Kathryn Chase
AU  - Charmian McIntyre
AU  - Frederick M. Boyce
AU  - Mary Campbell
AU  - Beth A. Cadigan
AU  - Lori Warzecki
AU  - Danilo A. Tagle
AU  - P. Hemachandra Reddy
AU  - Carlos Cepeda
AU  - Christopher R. Calvert
AU  - Eve S. Jokel
AU  - Gloria J. Klapstein
AU  - Marjorie A. Ariano
AU  - Michael S. Levine
AU  - Marian DiFiglia
AU  - Neil Aronin
TI  - Changes in Cortical and Striatal Neurons Predict Behavioral and Electrophysiological Abnormalities in a Transgenic Murine Model of Huntington's Disease
AID  - 10.1523/JNEUROSCI.21-23-09112.2001
DP  - 2001 Dec 01
TA  - The Journal of Neuroscience
PG  - 9112--9123
VI  - 21
IP  - 23
4099  - http://www.jneurosci.org/content/21/23/9112.short
4100  - http://www.jneurosci.org/content/21/23/9112.full
SO  - J. Neurosci.2001 Dec 01; 21
AB  - Neurons in Huntington's disease exhibit selective morphological and subcellular alterations in the striatum and cortex. The link between these neuronal changes and behavioral abnormalities is unclear. We investigated relationships between essential neuronal changes that predict motor impairment and possible involvement of the corticostriatal pathway in developing behavioral phenotypes. We therefore generated heterozygote mice expressing the N-terminal one-third of huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. The HD mice exhibited motor deficits between 3 and 10 months. The age of onset depended on an expanded polyglutamine length; phenotype severity correlated with increasing age. Neuronal changes in the striatum (nuclear inclusions) preceded the onset of phenotype, whereas cortical changes, especially the accumulation of huntingtin in the nucleus and cytoplasm and the appearance of dysmorphic dendrites, predicted the onset and severity of behavioral deficits. Striatal neurons in the HD mice displayed altered responses to cortical stimulation and to activation by the excitotoxic agent NMDA. Application of NMDA increased intracellular Ca2+ levels in HD100 neurons compared with wild-type neurons. Results suggest that motor deficits in Huntington's disease arise from cumulative morphological and physiological changes in neurons that impair corticostriatal circuitry.