title: Widespread state-dependent shifts in cerebellar activity in locomoting mice.
abstract: Excitatory drive enters the cerebellum via mossy fibers, which activate granule cells, and climbing fibers, which activate Purkinje cell dendrites. Until now, the coordinated regulation of these pathways has gone unmonitored in spatially resolved neuronal ensembles, especially in awake animals. We imaged cerebellar activity using functional two-photon microscopy and extracellular recording in awake mice locomoting on an air-cushioned spherical treadmill. We recorded from putative granule cells, molecular layer interneurons, and Purkinje cell dendrites in zone A of lobule IV/V, representing sensation and movement from trunk and limbs. Locomotion was associated with widespread increased activity in granule cells and interneurons, consistent with an increase in mossy fiber drive. At the same time, dendrites of different Purkinje cells showed increased co-activation, reflecting increased synchrony of climbing fiber activity. In resting animals, aversive stimuli triggered increased activity in granule cells and interneurons, as well as increased Purkinje cell co-activation that was strongest for neighboring dendrites and decreased smoothly as a function of mediolateral distance. In contrast with anesthetized recordings, no 1-10 Hz oscillations in climbing fiber activity were evident. Once locomotion began, responses to external stimuli in all three cell types were strongly suppressed. Thus climbing and mossy fiber representations can shift together within a fraction of a second, reflecting in turn either movement-associated activity or external stimuli.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Ilker
authors.initials: I
authors.lastname: Ozden
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Dombeck
authors.forename: Tycho M
authors.initials: TM
authors.lastname: Hoogland
authors.forename: David W
authors.initials: DW
authors.lastname: Tank
authors.forename: Samuel S-H
authors.initials: SS
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D021621:Imaging, Three-Dimensional; D007395:Interneurons / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D008124:Locomotion / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010812:Physical Stimulation; D011689:Purkinje Cells / Q000502:physiology; D012146:Rest; D014851:Wakefulness / Q000502:physiology
chemical_list: D002118:Calcium