Evidence that Climbing Fibers Control an Intrinsic Spike Generator in Cerebellar Purkinje Cells

Cerminara, Nadia L.; Rawson, John A

doi:10.1523/jneurosci.4530-03.2004

Cited by 138 publications

(141 citation statements)

References 41 publications

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“…Previous electrophysiological recording in isolated/slice preparations or in anesthetized animals indicated that Purkinje cells fire spontaneously in the absence of synaptic input (32)(33)(34). In contrast to these findings, blockade of granule cell transmission abolished firing of simple spikes in the DOX-treated awake animals.…”

Section: Discussionmentioning

confidence: 90%

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Wada

Kishimoto

Watanabe

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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), the authors note that in Fig. 2a, the same trace was inadvertently used for the electrophysiological records of RNB (DOXuntreated) and RNB (DOX-withdrawn). This error does not affect the conclusions of the article. The corrected figure and its legend appear below. (e and f ) Mean Ϯ SEM of firing rates of simple spikes (e) and complex spikes ( f) are shown with columns and bars, respectively. *** , P Ͻ 0.001 (comparison between DOX-treated RNB mice and all five other animals by the Scheffé test). (g) The extracellular recording site (red) was confirmed at the Purkinje cell layer by fluorescent Nissl staining. ML, molecular layer; PL, Purkinje cell layer; GL, granule cell layer. eyeblink conditioning ͉ interpositus nucleus ͉ Purkinje cell ͉ reversible neurotransmission blockade ͉ synaptic plasticity C lassical conditioning of the eyeblink reflex is elicited by paired presentation of conditioned stimulus (CS) with reinforcing unconditioned stimulus (US) (1-4). This associative motor learning is a basic form of cerebellum-dependent leaning. In eyeblink conditioning, the CS pathway includes the pontine nucleus and mossy fibers, whereas the US pathway includes the inferior olive and the climbing fibers (1-5). The mossy fibers project directly to the interpositus nucleus and indirectly to the cerebellar cortex via granule cells (1-5). The CS and US signals are thus conveyed to both the cerebellar cortex and the interpositus nucleus (Fig. 1a). The localization and underlying mechanisms of eyeblink conditioning have been extensively studied by different approaches including gene targeting (6-11), lesioning (12-15), mutant analysis (16), and pharmacological inactivation analyses (17-23). On the basis of these studies, one model proposes an essential role of the cerebellar Purkinje cell circuit in memory traces (24)(25)(26). According to this model, convergence of the CS and US signals induces long-term depression at the parallel fiber-Purkinje cell synapses. Because Purkinje cells are inhibitory, long-term depression causes a disinhibition of the interpositus nucleus and an increased input in the downstream motor pathways. The other model proposes that the memory trace is located in the interpositus nucleus and that conditioned responses (CRs) are properly evoked in response to CS by a timing signal from Purkinje cells (1,3,27,28). Eyeblink conditioning involves multiple learning processes, at least acquisition, expression, and storage of motor learning. Once the expression process of memory traces is impaired, it becomes difficult to define the key neural circuits responsible for expression, formation, and storage of memory traces.In this investigation, we adopted a novel reversible neurotransmission blocking (RNB) technique to explore the role of Purkinje cells and the interpositus nucleus in associative eyeblink conditioning. In the RNB transgenic mice, the tetanus toxin light chain is restrictedly expressed in granule cells under the control of a tetracycline-controlled reverse transactivator (rtTA) (29). Tetanus t...

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Section: Discussionmentioning

confidence: 90%

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Wada

Kishimoto

Watanabe

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Individual simple spikes are relatively ineffective at shunting ongoing synaptic potentials in Purkinje cells (Häusser et al, 2001), and thus the large synaptic and intrinsic conductances underlying the complex spike can provide a much more effective reset of synaptic integration. The wide range of spikelet numbers and frequencies possible at the soma, and their sensitivity to background excitation, may provide a more graded signal to fine-tune homeostatic mechanisms in the dendrites and proximal region of the axon (Cerminara and Rawson, 2004). Furthermore, because spikes are energetically expensive (Attwell and Laughlin, 2001), particularly when propagating over long distances, the limit on axonal firing may represent a protective mechanism to reduce the overall energetic costs of complex spike firing.…”

Section: Functional Implicationsmentioning

confidence: 99%

Determinants of Action Potential Propagation in Cerebellar Purkinje Cell Axons

Monsivais¹,

Clark²,

Roth³

et al. 2005

J. Neurosci.

141

185

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Axons have traditionally been viewed as highly faithful transmitters of action potentials. Recently, however, experimental evidence has accumulated to support the idea that under some circumstances axonal propagation may fail. Cerebellar Purkinje neurons fire highfrequency simple spikes, as well as bursts of spikes in response to climbing fiber activation (the "complex spike"). Here we have visualized the axon of individual Purkinje cells to directly investigate the relationship between somatic spikes and axonal spikes using simultaneous somatic whole-cell and cell-attached axonal patch-clamp recordings at 200 -800 m from the soma. We demonstrate that sodium action potentials propagate at frequencies up to ϳ260 Hz, higher than simple spike rates normally observed in vivo. Complex spikes, however, did not propagate reliably, with usually only the first and last spikes in the complex spike waveform being propagated. On average, only 1.7 Ϯ 0.2 spikes in the complex spike were propagated during resting firing, with propagation limited to interspike intervals above ϳ4 msec. Hyperpolarization improved propagation efficacy without affecting total axonal spike number, whereas strong depolarization could abolish propagation of the complex spike. These findings indicate that the complex spike waveform is not faithfully transmitted to downstream synapses and that propagation of the climbing fiber response may be modulated by background activity.

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“…We found a correlation between the average rate of the CFR and the number of EPSP components in a CFR, but whether the number of climbing fiber intraburst spikes plays a role in short-term changes in simple spike activity is not known. Such a function, if it exists, may also complement the role of climbing fibers in regulating the level of Purkinje cell simple spike firing (Colin et al, 1980;Cerminara and Rawson, 2004).…”

Section: Functions Of Climbing Fiber Burstsmentioning

confidence: 99%

Intraburst and Interburst Signaling by Climbing Fibers

Maruta

Hensbroek²,

Simpson³

2007

J. Neurosci.

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Although cerebellar Purkinje cell complex spikes occur at low frequency (ϳ1/s), each complex spike is often associated with a highfrequency burst (ϳ500/s) of climbing fiber spikes. We examined the possibility that signals are present within the climbing fiber bursts. By intracellularly recording from depolarized, nonspiking Purkinje cells in anesthetized pigmented rabbits, climbing fiber burst patterns were investigated by determining the number of components in the induced compound EPSPs during spontaneous activity and during visual stimulation. For our sample of 43 cells, Ͼ70% of all EPSPs were of the compound type composed of two or three EPSPs. During spontaneous activity, the number of components in each compound EPSP was not related to the latency to the succeeding compound EPSP. Conversely, the number of components in each compound EPSP was related to its latency after the preceding compound EPSP. This latency increased from 0.62 s for one-component EPSPs to 1.69 s for compound EPSPs with four or more components. The effect of visual stimulation on the climbing fiber activity was studied in 19 floccular Purkinje cells whose low-frequency interburst climbing fiber response was modulated by movement about the vertical axis. During sinusoidal oscillation (0.1 Hz, Ϯ10°), compound EPSPs with a larger number of components tended to be more prevalent during movement in the excitatory direction than in the inhibitory direction. Thus, climbing fibers can, in addition to modulation of their low interburst frequency, transmit signals in the form of the number of spikes within each high-frequency burst.

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Evidence that Climbing Fibers Control an Intrinsic Spike Generator in Cerebellar Purkinje Cells

Cited by 138 publications

References 41 publications

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Determinants of Action Potential Propagation in Cerebellar Purkinje Cell Axons

Intraburst and Interburst Signaling by Climbing Fibers

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