title: Integration of Purkinje cell inhibition by cerebellar nucleo-olivary neurons.
abstract: Neurons in the cerebellar cortex, cerebellar nuclei, and inferior olive (IO) form a trisynaptic loop critical for motor learning. IO neurons excite Purkinje cells via climbing fibers and depress their parallel fiber inputs. Purkinje cells inhibit diverse cells in the cerebellar nuclei, including small GABAergic nucleo-olivary neurons that project to the IO. To investigate how these neurons integrate synaptic signals from Purkinje cells, we retrogradely labeled nucleo-olivary cells in the contralateral interpositus and lateral nuclei with cholera toxin subunit B-Alexa Fluor 488 and recorded their electrophysiological properties in cerebellar slices from weanling mice. Nucleo-olivary cells fired action potentials over a relatively narrow dynamic range (maximal rate, ∼ 70 spikes/s), unlike large cells that project to premotor areas (maximal rate, ∼ 400 spikes/s). GABA(A) receptor-mediated IPSCs evoked by electrical or optogenetic stimulation of Purkinje cells were more than 10-fold slower in nucleo-olivary cells (decay time, ∼ 25 ms) than in large cells (∼ 2 ms), and repetitive stimulation at 20-150 Hz evoked greatly summating IPSCs. Nucleo-olivary firing rates varied inversely with IPSP frequency, and the timing of Purkinje IPSPs and nucleo-olivary spikes was uncorrelated. These attributes contrast with large cells, whose brief IPSCs and rapid firing rates can permit well timed postinhibitory spiking. Thus, the intrinsic and synaptic properties of these two projection neurons from the cerebellar nuclei tailor them for differential integration and transmission of their Purkinje cell input.
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208.
authors.forename: Marion
authors.initials: M
authors.lastname: Najac
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208 i-raman@northwestern.edu.
authors.forename: Indira M
authors.initials: IM
authors.lastname: Raman
mesh_terms: D000200:Action Potentials; D000818:Animals; D059330:GABAergic Neurons / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D009847:Olivary Nucleus / Q000166:cytology / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*
keywords: IPSC; IPSP; cerebellum; deep cerebellar nuclei; inferior olive