Time and Frequency Characteristics of Purkinje Cell Complex Spikes in the Awake Monkey Performing a Nonperiodic Task

A number of studies have been interpreted to support the view that the inferior olive climbing fibers send periodic signals to the cerebellum to time and pace behavior. In a direct test of this hypothesis in macaques performing nonperiodic tasks, we analyzed continuous recordings of complex spikes from the lateral cerebellar hemisphere. We found no periodicity outside of a 100-ms relative refractory period.

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Developmental Changes in Evoked Purkinje Cell Complex Spike Responses

Journal of Neurophysiology ◽

10.1152/jn.00481.2003 ◽

2003 ◽

Vol 90 (4) ◽

pp. 2349-2357 ◽

Cited By ~ 10

Author(s):

Daniel A. Nicholson ◽

John H. Freeman

Keyword(s):

Motor Learning ◽

Purkinje Cell ◽

Inferior Olive ◽

Cell Complex ◽

Climbing Fibers ◽

Somatosensory Stimulation ◽

Complex Spike ◽

Long Latency ◽

Inhibitory Feedback ◽

Complex Spikes

The development of synaptic interconnections between the cerebellum and inferior olive, the sole source of climbing fibers, could contribute to the ontogeny of certain forms of motor learning (e.g., eyeblink conditioning). Purkinje cell complex spikes are produced exclusively by climbing fibers and exhibit short- and long-latency activity in response to somatosensory stimulation. Previous studies have demonstrated that evoked short- and long-latency complex spikes generally occur on separate trials and that this response segregation is regulated by inhibitory feedback to the inferior olive. The present experiment tested the hypothesis that complex spikes evoked by periorbital stimulation are regulated by inhibitory feedback from the cerebellum and that this feedback develops between postnatal days (PND) 17 and 24. Recordings from individual Purkinje cell complex spikes in urethan-anesthetized rats indicated that the segregation of short- and long-latency evoked complex spike activity emerges between PND17 and PND24. In addition, infusion of picrotoxin, a GABAA-receptor antagonist, into the inferior olive abolished the response pattern segregation in PND24 rats, producing evoked complex spike response patterns similar to those characteristic of younger rats. These data support the view that cerebellar feedback to the inferior olive, which is exclusively inhibitory, undergoes substantial changes in the same developmental time window in which certain forms of motor learning emerge.

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Association Between Dendritic Lamellar Bodies and Complex Spike Synchrony in the Olivocerebellar System

Journal of Neurophysiology ◽

10.1152/jn.1997.77.4.1747 ◽

1997 ◽

Vol 77 (4) ◽

pp. 1747-1758 ◽

Cited By ~ 45

Author(s):

C. I. De Zeeuw ◽

S.K.E. Koekkoek ◽

D.R.W. Wylie ◽

J. I. Simpson

Keyword(s):

Purkinje Cell ◽

Gap Junctions ◽

Purkinje Cells ◽

Inferior Olive ◽

Cerebellar Nuclei ◽

Climbing Fibers ◽

Lamellar Bodies ◽

Spike Synchrony ◽

Complex Spike ◽

Simple Spike

De Zeeuw, C. I., S.K.E. Koekkoek, D.R.W. Wylie, and J. I. Simpson. Association between dendritic lamellar bodies and complex spike synchrony in the olivocerebellar system. J. Neurophysiol. 77: 1747–1758, 1997. Dendritic lamellar bodies have been reported to be associated with dendrodendritic gap junctions. In the present study we investigated this association at both the morphological and electrophysiological level in the olivocerebellar system. Because cerebellar GABAergic terminals are apposed to olivary dendrites coupled by gap junctions, and because lesions of cerebellar nuclei influence the coupling between neurons in the inferior olive, we postulated that if lamellar bodies and gap junctions are related, then the densities of both structures will change together when the cerebellar input is removed. Lesions of the cerebellar nuclei in rats and rabbits resulted in a reduction of the density of lamellar bodies, the number of lamellae per lamellar body, and the density of gap junctions in the inferior olive, whereas the number of olivary neurons was not significantly reduced. The association between lamellar bodies and electrotonic coupling was evaluated electrophysiologically in alert rabbits by comparing the occurrence of complex spike synchrony in different Purkinje cell zones of the flocculus that receive their climbing fibers from olivary subnuclei with different densities of lamellar bodies. The complex spike synchrony of Purkinje cell pairs, that receive their climbing fibers from an olivary subnucleus with a high density of lamellar bodies, was significantly higher than that of Purkinje cells, that receive their climbing fibers from a subnucleus with a low density of lamellar bodies. To investigate whether the complex spike synchrony is related to a possible synchrony between simple spikes, we recorded simultaneously the complex spike and simple spike responses of Purkinje cell pairs during natural visual stimulation. Synchronous simple spike responses did occur, and this synchrony tended to increase as the synchrony between the complex spikes increased. This relation raises the possibility that synchronously activated climbing fibers evoke their effects in part via the simple spike response of Purkinje cells. The present results indicate that dendritic lamellar bodies and dendrodendritic gap junctions can be downregulated concomitantly, and that the density of lamellar bodies in different olivary subdivisions is correlated with the degree of synchrony of their climbing fiber activity. Therefore these data support the hypothesis that dendritic lamellar bodies can be associated with dendrodendritic gap junctions. Considering that the density of dedritic lamellar bodies in the inferior olive is higher than in any other area of the brain, this conclusion implies that electrotonic coupling is important for the function of the olivocerebellar system.

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Conversion of graded presynaptic climbing fiber activity into graded postsynaptic Ca2+ signals by Purkinje cell dendrites

10.1101/423491 ◽

2018 ◽

Author(s):

Michael A. Gaffield ◽

Jason M. Christie

Keyword(s):

Purkinje Cell ◽

Inferior Olive ◽

Mossy Fiber ◽

Climbing Fiber ◽

Climbing Fibers ◽

Dependent Manner ◽

Related Information ◽

External Stimuli ◽

Purkinje Cell Dendrites

AbstractThe brain must make sense of external stimuli to generate relevant behavior. We used a combination of in vivo approaches to investigate how the cerebellum processes sensory-related information. We found that the inferior olive encodes contexts of sensory-associated external cues in a graded manner, apparent in the presynaptic activity of their axonal projections in the cerebellar cortex. Further, individual climbing fibers were broadly responsive to different sensory modalities but relayed sensory-related information to the cortex in a lobule-dependent manner. Purkinje cell dendrites faithfully transformed this climbing fiber activity into dendrite-wide Ca2+ signals without a direct contribution from the mossy fiber pathway. These results demonstrate that the size of climbing fiber-evoked Ca2+ signals in Purkinje cell dendrites is largely determined by the firing level of climbing fibers. This coding scheme emphasizes the overwhelming role of the inferior olive in generating salient signals useful for instructing plasticity and learning.

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The induction of multiple cell cycle events precedes target-related neuronal death

Development ◽

10.1242/dev.121.8.2385 ◽

1995 ◽

Vol 121 (8) ◽

pp. 2385-2395 ◽

Cited By ~ 1

Author(s):

K. Herrup ◽

J.C. Busser

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Purkinje Cell ◽

Inferior Olive ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Ventricular Zone ◽

Nuclear Antigen ◽

Electron Microscopic ◽

Related Cell

Unexpected nerve cell death has been reported in several experimental situations where neurons have been forced to re-enter the cell cycle after leaving the ventricular zone and entering the G0, non-mitotic stage. To determine whether an association between cell death and unscheduled cell cycling might be found in conjunction with any naturally occurring developmental events, we have examined target-related cell death in two neuronal populations, the granule cells of the cerebellar cortex and the neurons of the inferior olive. Both of these cell populations have a demonstrated developmental dependency on their synaptic target, the cerebellar Purkinje cell. Two mouse neurological mutants, staggerer (sg/sg) and lurcher (+/Lc), are characterized by intrinsic Purkinje cell deficiencies and, in both mutants, substantial numbers of cerebellar granule cells and inferior olive neurons die due to the absence of trophic support from their main postsynaptic target. We report here that the levels of three independent cell cycle markers--cyclin D, proliferating cell nuclear antigen and bromodeoxyuridine incorporation--are elevated in the granule cells before they die. Although lurcher Purkinje cells die during a similar developmental period, no compelling evidence for any cell cycle involvement in this instance of pre-programmed cell death could be found. While application of the TUNEL technique (in situ terminal transferase end-labeling of fragmented DNA) failed to label dying granule cells in either mutant, light and electron microscopic observations are consistent with the interpretation that the death of these cells is apoptotic in nature. Together, the data indicate that target-related cell death in the developing central nervous system is associated with a mechanism of cell death that involves an apparent loss of cell cycle control.

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Motor Coding in Floccular Climbing Fibers

Journal of Neurophysiology ◽

10.1152/jn.01191.2005 ◽

2006 ◽

Vol 95 (4) ◽

pp. 2342-2351 ◽

Cited By ~ 21

Author(s):

Beerend Winkelman ◽

Maarten Frens

Keyword(s):

Visual Motion ◽

Inferior Olive ◽

Motor Behavior ◽

Climbing Fibers ◽

Retinal Slip ◽

Motor Component ◽

Prepositus Hypoglossi ◽

Sensorimotor Information ◽

Sensory Encoding ◽

Oculomotor Learning

The climbing fibers (CFs) that project from the dorsal cap of the inferior olive (IO) to the flocculus of the cerebellar cortex have been reported to be purely sensory, encoding “retinal slip.” However, a clear oculomotor projection from the nucleus prepositus hypoglossi (NPH) to the IO has been shown. We therefore studied the sensorimotor information that is present in the CF signal. We presented rabbits with visual motion noise stimuli to break up the tight relation between instantaneous retinal slip and eye movement. Strikingly, the information about the motor behavior in the CF signal more than doubled that of the sensory component and was time-locked more tightly. The contribution of oculomotor signals was independently confirmed by analysis of spontaneous eye movements in the absence of visual input. The motor component of the CF code is essential to distinguish unexpected slip from self-generated slip, which is a prerequisite for proper oculomotor learning.

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Anodal Excitation of Cardiac Muscle

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1957.190.2.383 ◽

1957 ◽

Vol 190 (2) ◽

pp. 383-390 ◽

Cited By ~ 94

Author(s):

Paul F. Cranefield ◽

Brian F. Hoffman ◽

Arthur A. Siebens

Keyword(s):

Cardiac Muscle ◽

Refractory Period ◽

Ventricular Myocardium ◽

Relative Refractory Period ◽

Double Origin ◽

Cathodal Stimulation

The strength-interval curve of dog ventricular myocardium has been measured with anodal and cathodal stimulation. During diastole the anodal threshold is higher than the cathodal. As anodal stimuli are applied progressively earlier the anodal threshold first rises above and then falls to levels below the anodal diastolic threshold. During most of the relative refractory period the anodal threshold is lower than the cathodal threshold. At all times during the late relative refractory period and throughout diastole excitation of double origin (anodal and cathodal) is evoked by sufficiently strong stimuli; this simultaneous origin of excitation at two points does not evoke fibrillation. During the early relative refractory period, however, only the anode is able to excite. Differences between anodal and cathodal thresholds are not attributable to asynchronous repolarization at the two electrode sites. The ‘no-response’ phenomenon occurs only when the anodal threshold is markedly lower than the cathodal.

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