title: GABAergic modulation of complex spike activity by the cerebellar nucleoolivary pathway in rat.
abstract: 1. The role of gamma-aminobutyric acid (GABA) on the pattern generation properties of neuronal ensembles in the olivocerebellar system was studied utilizing multiple electrode recordings of complex spikes (CSs) from rat crus 2a Purkinje cells (PCs). Initially multiple electrode experiments were combined with microinjections of picrotoxin into the inferior olive (IO). To corroborate the picrotoxin findings, the cerebellar nuclei, a major source of the GABAergic terminals in the IO, were chemically lesioned with the use of microinjections of kainic acid and N-methyl-D-aspartate. Both procedures generated comparable results. 2. After intraolivary picrotoxin injection there was an increase in the average firing rate, synchrony, and rhythmicity of spontaneous CS activity. In addition, the neuronal oscillation frequency tended to shift to lower frequencies. 3. The spatial distribution of synchronous CS activity in control conditions displayed a predominantly rostrocaudal orientation. Injection of picrotoxin to the IO disrupted this rostrocaudal organization and led to synchronous CS activity among PCs throughout crus 2a. Similar effects were observed relating to the distribution of CSs evoked via the "climbing fiber reflex," in which antidromic activation of the climbing fibers is followed by a return excitation that is mediated by the gap junctions between olivary neurons. 4. Chemical lesions of the cerebellar nuclei resulted in increased CS average firing rates. The effect of the lesions on CS synchronicity was similar to that following the picrotoxin injections, but greater in magnitude. In contrast to the olivary picrotoxin injections, the cerebellar nuclear lesions did not lead to an enhanced CS rhythmicity. 5. Bilateral recordings from left and right crus 2a demonstrated significant interhemispheric synchronization of CS activity, consistent with a previous report. Both unilateral olivary injections of picrotoxin and unilateral cerebellar nuclear lesions resulted in increased synchronization of CS activity between the left and right crus 2a. 6. We conclude that the cerebellar nucleoolivary projection to the olivary glomeruli modulates the effective electrotonic coupling between olivary neurons, and thereby carves out ensembles of neurons whose activity is synchronized. Thus these two nuclei may form the basis for a flexible and sophisticated motor coordination system able to help generate the many distinct movements that organisms are capable of performing.
authors.affiliation: Department of Physiology and Neuroscience, New York University Medical Center, New York 10016, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lang
authors.forename: I
authors.initials: I
authors.lastname: Sugihara
authors.forename: R
authors.initials: R
authors.lastname: Llinás
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D002529:Cerebellar Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005246:Feedback; D007839:Functional Laterality / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009847:Olivary Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018756:GABA Antagonists; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid