title: Multiple types of cerebellar target neurons and their circuitry in the vestibulo-ocular reflex.
abstract: The cerebellum influences behavior and cognition exclusively via Purkinje cell synapses onto neurons in the deep cerebellar and vestibular nuclei. In contrast with the rich information available about the organization of the cerebellar cortex and its synaptic inputs, relatively little is known about microcircuitry postsynaptic to Purkinje cells. Here we examined the cell types and microcircuits through which Purkinje cells influence an oculomotor behavior controlled by the cerebellum, the horizontal vestibulo-ocular reflex, which involves only two eye muscles. Using a combination of anatomical tracing and electrophysiological recordings in transgenic mouse lines, we identified several classes of neurons in the medial vestibular nucleus that receive Purkinje cell synapses from the cerebellar flocculus. Glycinergic and glutamatergic flocculus target neurons (FTNs) with somata densely surrounded by Purkinje cell terminals projected axons to the ipsilateral abducens and oculomotor nuclei, respectively. Of three additional types of FTNs that were sparsely innervated by Purkinje cells, glutamatergic and glycinergic neurons projected to the contralateral and ipsilateral abducens, respectively, and GABAergic neurons projected to contralateral vestibular nuclei. Densely innervated FTNs had high spontaneous firing rates and pronounced postinhibitory rebound firing, and were physiologically homogeneous, whereas the intrinsic excitability of sparsely innervated FTNs varied widely. Heterogeneity in the molecular expression, physiological properties, and postsynaptic targets of FTNs implies that Purkinje cell activity influences the neural control of eye movements in several distinct ways. These results indicate that the cerebellum regulates a simple reflex behavior via at least five different cell types that are postsynaptic to Purkinje cells.
authors.affiliation: Salk Institute for Biological Studies and Howard Hughes Medical Institute, La Jolla, California 92037, USA.
authors.forename: Minyoung
authors.initials: M
authors.lastname: Shin
authors.forename: Setareh H
authors.initials: SH
authors.lastname: Moghadam
authors.forename: Chris
authors.initials: C
authors.lastname: Sekirnjak
authors.forename: Martha W
authors.initials: MW
authors.lastname: Bagnall
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Kolkman
authors.forename: Richard
authors.initials: R
authors.lastname: Jacobs
authors.forename: Michael
authors.initials: M
authors.lastname: Faulstich
authors.forename: Sascha
authors.initials: S
authors.lastname: du Lac
mesh_terms: D000818:Animals; D001703:Biophysics; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D064026:Calbindins; D002531:Cerebellum / Q000166:cytology* / Q000648:ultrastructure; D003911:Dextrans / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009415:Nerve Net / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology*; D012235:Rhodamines / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology; D014726:Vestibular Nuclei / Q000166:cytology / Q000502:physiology; D016875:tau Proteins / Q000235:genetics
chemical_list: D064026:Calbindins; D003911:Dextrans; C067661:Fluoro-Ruby; D050487:Glycine Plasma Membrane Transport Proteins; D008164:Luminescent Proteins; D012235:Rhodamines; D064030:S100 Calcium Binding Protein G; C493270:Slc6a5 protein, mouse; C076397:biotinylated dextran amine; D016875:tau Proteins; D001710:Biotin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2