title: GABAergic and glutamatergic modulation of spontaneous and motor-cortex-evoked complex spike activity.
abstract: Olivocerebellar activity is organized such that synchronous complex spikes occur primarily among Purkinje cells located within the same parasagittally oriented strip of cortex. Previous findings have shown that this synchrony distribution is modulated by the release of GABA and glutamate within the inferior olive, which probably act by controlling the efficacy of the electrotonic coupling between olivary neurons. The relative strengths of these two neurotransmitters in modulating the patterns of synchrony were compared by obtaining multiple electrode recordings of spontaneous crus 2a complex spike activity during intraolivary injection of solutions containing a GABA(A) (picrotoxin) and/or AMPA [1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX)] receptor antagonist. Injection of either antagonist led to increased synchrony between cells located within the same parasagittally oriented approximately 250-microm-wide cortical strip. Picrotoxin also increased complex spike synchrony among cells located in different cortical strips, leading to a less prominent banding pattern, whereas injections of NBQX tended to decrease complex spike synchrony among such cells, enhancing the banding pattern. The relative strength of these two classes of olivary afferents was assessed by first injecting one of the antagonists alone and then in combination with the other. The enhanced banding pattern of complex spike synchrony following injection of NBQX alone remained during the subsequent combined injection of both antagonists. Furthermore, the widespread synchronization of complex spike activity following injection of picrotoxin alone was partially or completely reversed by combined injection of picrotoxin and NBQX. Changes in the climbing fiber reflex induced by the intraolivary injections paralleled the changes observed for spontaneous complex spike activity, indicating that the effects of picrotoxin and NBQX on the synchrony distribution reflect changes in the pattern of effective coupling of inferior olivary neurons and demonstrating that synchronous complex spike activity does not require simultaneous excitatory input to olivary cells. Finally the pattern of synchrony during motor cortical stimulation was examined. It was found that the patterns of synchrony for motor-cortex-evoked complex spike activity were similar to those of spontaneous activity, indicating an important role for electrotonic coupling in determining the response of the olivocerebellar system to afferent input. Moreover, intraolivary injections of picrotoxin increased the spatial distribution of the evoked response. In sum, the results provide evidence for the hypothesis that electrotonic coupling of inferior olivary neurons via gap junctions is the mechanism underlying complex spike synchrony and that this coupling plays an important role in determining the responses of the olivocerebellar system to synaptic input.
authors.affiliation: Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA. Lange01@popmail.med.nyu.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002531:Cerebellum / Q000502:physiology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D009044:Motor Cortex / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D009847:Olivary Nucleus / Q000166:cytology / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D010852:Picrotoxin; D011810:Quinoxalines; D005680:gamma-Aminobutyric Acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline