Characterizing Purkinje Cell Responses and Cerebellar Influence on Fluid Licking in the Mouse

Abstract

DEDICATIONThis dissertation is dedicated to my husband and son, David and Ari Wilcox, for their love and support in helping me to achieve a major goal.iv ACKNOWLEDGEMENTS I would like to acknowledge everyone contributing to my completion of my dissertation. My research advisor, Dr. Detlef Heck, has truly been an important force in my perseverance through timely advice, patience, and his willingness to serve as a mentor in all aspects of my development as an independent researcher. I would like to thank Snigdha Roy for the ample assistance, numerous reviews of my texts, and friendship. ABSTRACTRodents consume water by performing stereotypical, rhythmic licking movements which are believed to be driven by central pattern generating circuits located in the brainstem. Temporal aspects of rhythmic licking behavior have been shown to be represented in the olivo-cerebellar system in the form of population complex spike activity. These findings suggest that the olivo-cerebellar system is involved in the generating circuitry responsible for licking rhythm in rodents. However, the representation of licking in the simple spike activity of Purkinje cells and the consequences of loss of cerebellar function on licking behavior has not been quantified. I investigated the influence of the cerebellum on the maintenance of rhythm in murine fluid-licking.In one set of experiments, I characterized Purkinje cell activity in healthy mice during fluid licking. Use of a head-restrained preparation allowed recordings of wellisolated single units during repeated experimental sessions. Thus, a large number of neurons were tested for their relationship with behavior and detailed spatial maps of behavior related neuronal activity were generated as exemplified here with recordings from lick-related Purkinje cells in the cerebellum. The data show a multifaceted representation of licking behavior in the simple spike activity of a large population of Purkinje cells distributed across Crus I, Crus II, and lobus simplex of mouse cerebellar cortex. Lick related Purkinje cell simple spike activity was changed in a manner that was either rhythmic, in phase with the lick rhythm, or nonrhythmic with a decrease or increase in firing in relation to licks but not phasically. For rhythmically responsive units, signal modulation was marked by the introduction of a phasic variation in the frequency of spikes. A subpopulation of lick related Purkinje cells exhibited different activity patterns during short and long interlick intervals (ILIs).I examined the role of the cerebellum in fluid-licking by using several models of cerebellar ataxia with distinct causes. First, I observed fluid-licking in animals over several days to determine how the microstructure of the behavior may also be altered. The first model involved animals that underwent cerebellectomies. Surgical removal of the cerebellum resulted in significant slowing of the lick rhythm but did not affect the mouse's ability to perform the gross licking movement. Thus, the cerebellum is involved in the...