altered neurocircuitry in the dopamine transporter knockout mouse brain多巴胺转运体基因敲除小鼠大脑的神经发生改变.pdfVIP

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain 1 1,2 1 3 3 1 Xiaowei Zhang , Elaine L. Bearer , Benoit Boulat , F. Scott Hall , George R. Uhl , Russell E. Jacobs * 1 Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America, 2 Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States of America, 3 Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, United States of America Abstract The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise s