Bistability of cerebellar Purkinje cells modulated by sensory stimulation

Loewenstein, Yonatan; Mahon, Séverine; Chadderton, Paul; Kitamura, Kazuhiro; Sompolinsky, Haim; Yarom, Yosef; Häusser, Michael

doi:10.1038/nn1393

Cited by 291 publications

(317 citation statements)

References 45 publications

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“…S2A). The spontaneous activity in vivo consisted of two types of responses: the characteristic SSs, which reflect an interplay between afferent synaptic activity (22,23) and intrinsic properties of PNs (24,25); and the complex spikes (CSs) (26), which are generated by the activity of the climbing fibers (Fig. S2B).…”

Section: Resultsmentioning

confidence: 99%

Disruption of the olivo-cerebellar circuit by Purkinje neuron-specific ablation of BK channels

Chen

Kovalchuk

Adelsberger

et al. 2010

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

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105

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The large-conductance voltage-and calcium-activated potassium (BK) channels are ubiquitously expressed in the brain and play an important role in the regulation of neuronal excitation. Previous work has shown that the total deletion of these channels causes an impaired motor behavior, consistent with a cerebellar dysfunction. Cellular analyses showed that a decrease in spike firing rate occurred in at least two types of cerebellar neurons, namely in Purkinje neurons (PNs) and in Golgi cells. To determine the relative role of PNs, we developed a cell-selective mouse mutant, which lacked functional BK channels exclusively in PNs. The behavioral analysis of these mice revealed clear symptoms of ataxia, indicating that the BK channels of PNs are of major importance for normal motor coordination. By using combined two-photon imaging and patch-clamp recordings in these mutant mice, we observed a unique type of synaptic dysfunction in vivo, namely a severe silencing of the climbing fiber-evoked complex spike activity. By performing targeted pharmacological manipulations combined with simultaneous patch-clamp recordings in PNs, we obtained direct evidence that this silencing of climbing fiber activity is due to a malfunction of the tripartite olivo-cerebellar feedback loop, consisting of the inhibitory synaptic connection of PNs to the deep cerebellar nuclei (DCN), followed by a projection of inhibitory DCN afferents to the inferior olive, the origin of climbing fibers. Taken together, our results establish an essential role of BK channels of PNs for both cerebellar motor coordination and feedback regulation in the olivo-cerebellar loop. cerebellar ataxia | climbing fiber | complex spike | two-photon imaging

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Section: Resultsmentioning

confidence: 99%

Disruption of the olivo-cerebellar circuit by Purkinje neuron-specific ablation of BK channels

Chen

Kovalchuk

Adelsberger

et al. 2010

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

Self Cite

105

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“…Therefore, we examined the mechanisms underlying the transition between two phases of the SWO cycle. In addition to network dynamics, the intrinsic properties of neurons play a fundamental role in governing cortical bistable activity (27). One possibility is that a K ϩ current activated by the metabolic demands ([ATP]:[ADP]) of network activity during the up phase of the oscillation may drive the transition to down phase.…”

Section: Resultsmentioning

confidence: 99%

Neuronal metabolism governs cortical network response state

Cunningham

Pervouchine

Racca

et al. 2006

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

163

151

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The level of arousal in mammals is correlated with metabolic state and specific patterns of cortical neuronal responsivity. In particular, rhythmic transitions between periods of high activity (up phases) and low activity (down phases) vary between wakefulness and deep sleep͞anesthesia. Current opinion about changes in cortical response state between sleep and wakefulness is split between neuronal network-mediated mechanisms and neuronal metabolism-related mechanisms. Here, we demonstrate that slow oscillations in network state are a consequence of interactions between both mechanisms. Specifically, recurrent networks of excitatory neurons, whose membrane potential is partly governed by ATPmodulated potassium (KATP) channels, mediate response-state oscillations via the interaction between excitatory network activity involving slow, kainate receptor-mediated events and the resulting activation of ATP-dependent homeostatic mechanisms. These findings suggest that K ATP channels function as an interface between neuronal metabolic state and network responsivity in mammalian cortex.glutamate ͉ slow-wave oscillation ͉ potassium channel ͉ rhythm S low-wave oscillations (SWO) occur in the cerebral cortex and associated areas (1). They are particularly manifest during periods of behavioral quiescence and are an ubiquitous feature of deep sleep (2-5). Two hypotheses dominate the possible functional significance of such activity (6). SWO have been shown to be critical for learning and plasticity (2, 7). Additionally it has been proposed that they allow for, or are generated by, reduced neuronal metabolism, whereby restorative cellular processes take place to reset the deficit induced by a period of wakefulness (8-10). At the cellular level, slow-wave electroencephalogram activity correlates with fluctuations in the membrane potential of cortical neurones (3, 11), where periods of hyperpolarization (down phase) alternate between periods of depolarization (up phase). Such bistable behavior is thought to depend on a balance of recurrent excitation and local inhibition (12, 13) in addition to slow-wave input from the thalamus (14). However, persistent depolarized states might also occur through synaptic excitation alone, with kinetically slow excitatory synaptic potentials (EPSPs) such as those generated by kainate receptors (15) or NMDA receptors (but see below), temporally summating with sufficient background activity (16). In addition, such a maintained depolarization can be generated purely by intrinsic ionic currents in bistable neurons (17).The nature of the relationship between neuronal metabolic state and SWO is also unclear. From a network perspective, a number of synaptic conductances, most notably those mediated by NMDA receptors (18), are modulated by metabolism. However, some neurons have intrinsic conductances specifically designed to sense aspects of metabolic state. During wakefulness, constant neuronal activity is metabolically demanding (8,19). Measurements of cerebral metabolism during slow-wave sleep have de...

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“…It is also possible that this network activity interacts with certain membrane properties and states of the cell. Our data do not enable us to address such compelling questions as whether the GPe pauses represent a bistable membrane phenomenon with ultrafast dynamics of channel gating, or which mechanisms are involved in their termination (Coombes and Bressloff, 2005;Loewenstein et al, 2005;Hashimoto and Kita, 2006;Schonewille et al, 2006;Izhikevich, 2007).…”

Section: Do the Pauses Have An Intrinsic Origin?mentioning

confidence: 89%

Statistical Properties of Pauses of the High-Frequency Discharge Neurons in the External Segment of the Globus Pallidus

Elias¹,

Joshua²,

Goldberg³

et al. 2007

J. Neurosci.

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The neurons of many basal ganglia nuclei, including the external and internal globus pallidus (GPe and GPi, respectively) and the substantia nigra pars reticulata (SNr) are characterized by their high-frequency (50 -100 spikes/s) tonic discharge (HFD). However, the high firing rate of GPe neurons is interrupted by long pauses. We studied the extracellularly recorded spiking activity of 212 well-isolated HFD GPe and 52 GPi/SNr neurons from five monkeys during different states of behavioral activity. An algorithm that maximizes the surprise function was used to detect pauses and pauser cells ("pausers"). Only 6% of the GPi/SNr neurons versus as many as 56% of the GPe neurons were classified as pausers. The GPe average pause duration equals 0.62 s. The interpause intervals follow a Poissonian distribution with a frequency of 13 pauses/minute. No linear relationship was found between pause parameters (duration or frequency) and the firing rate of the cell. Pauses were preceded by various changes in firing rate but not dominantly by a decrease. The average amplitude and duration of the spike waveform was modulated only after the pause but not before it. Pauses of pairs of cells that were recorded simultaneously were not correlated. The probability of GPe cells to pause spontaneously was extremely variable among monkeys (30 -90%) and inversely related to the degree of the monkey's motor activity. These findings suggest that spontaneous GPe pauses are related to low-arousal periods and are generated by a process that is independent of the discharge properties of the cells.

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Bistability of cerebellar Purkinje cells modulated by sensory stimulation

Cited by 291 publications

References 45 publications

Disruption of the olivo-cerebellar circuit by Purkinje neuron-specific ablation of BK channels

Disruption of the olivo-cerebellar circuit by Purkinje neuron-specific ablation of BK channels

Neuronal metabolism governs cortical network response state

Statistical Properties of Pauses of the High-Frequency Discharge Neurons in the External Segment of the Globus Pallidus

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