Electrophysiology of guinea‐pig cerebellar nuclear cells in the in vitro brain stem‐cerebellar preparation.

Llinás, Rodolfó R.; Mühlethaler, Michel

doi:10.1113/jphysiol.1988.sp017288

Cited by 352 publications

(239 citation statements)

References 31 publications

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“…3 A and B). A similar phenomenon has previously been reported at the synapse formed between Purkinje cells and deep cerebellar nuclei (26)(27)(28). However, if the Purkinje cell was already in an up state when the GABA A conductance occurred, the resulting IPSP caused a deep hyperpolarization of the cell membrane beyond the reversal potential for GABA.…”

Section: Discussionsupporting

confidence: 83%

Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states

Oldfield

Marty

Stell

2010

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

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We demonstrate that single interneurons can toggle the output neurons of the cerebellar cortex (the Purkinje cells) between their two states. The firing of Purkinje cells has previously been shown to alternate between an "up" state in which the cell fires spontaneous action potentials and a silent "down" state. We show here that small hyperpolarizing currents in Purkinje cells can bidirectionally toggle Purkinje cells between down and up states and that blockade of the hyperpolarization-activated cation channels (H channels) with the specific antagonist ZD7288 (10 μM) blocks the transitions from down to up states. Likewise, hyperpolarizing inhibitory postsnyaptic potentials (IPSPs) produced by small bursts of action potentials (10 action potentials at 50 Hz) in molecularlayer interneurons induce these bidirectional transitions in Purkinje cells. Furthermore, single interneurons in paired interneuron → Purkinje cell recordings, produce bidirectional switches between the two states of Purkinje cells. The ability of molecular-layer interneurons to toggle Purkinje cells occurs when Purkinje cells are recorded under whole-cell patch-clamp conditions as well as when action potentials are recorded in an extracellular loose cell-attached configuration. The mode switch demonstrated here indicates that a single presynaptic interneuron can have opposite effects on the output of a given Purkinje cell, which introduces a unique type of synaptic interaction that may play an important role in cerebellar signaling.A s the sole output of the cerebellar cortex, Purkinje cells are ultimately responsible for relaying the computation performed by the entire network. Even though membrane properties and synaptic currents have been extensively studied in the cerebellar circuit, it still remains unclear how Purkinje cells process information coming from the rest of the cerebellar cortex before passing it on to the deep cerebellar nuclei. Purkinje cells are known to intrinsically generate action potentials at high rates and also to have an intrinsic membrane bistability (1-4). The cell switches between hyperpolarized potentials during which it is silent and depolarized potentials during which it fires action potentials (1, 2, 5-11). The frequency of changes between the two states in awake versus anesthetized animals in vivo has been disputed, but it is agreed that the bistability exists in a fraction of Purkinje cells in both anesthetized and unanesthetized animals (5, 6). This unique characteristic of the output of Purkinje cells potentially plays a significant role in passing the computation of the cerebellar cortex onto the cerebellar nuclei. Therefore to understand how Purkinje cells process this information it is essential to understand how the cells within the cerebellar cortex influence this bistable output of Purkinje cells.The climbing fibers, which provide glutamatergic inputs to Purkinje cells from outside the cerebellar cortex, have been shown to produce complex spikes in Purkinje cells (1). In experiments performed in vivo a...

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Section: Discussionsupporting

confidence: 83%

Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states

Oldfield

Marty

Stell

2010

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

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“…Despite their important location, little is known about the biophysical mechanisms underlying their activity (Sastry et al, 1997). When isolated, these cells fire spontaneous action potentials similar to those in intact preparations (Thach, 1968;Jahnsen, 1986a;Llinás and Mühlethaler, 1988;Mouginot and Gähwiler, 1995;Aizenman and Linden, 1999) and therefore provide reasonable models for studying firing. Importantly, isolated cells allow for quantitative measurements of the pharmacology and kinetics of the ionic currents intrinsic to these neurons, which previously have not been studied under voltage clamp.…”

Section: Discussionmentioning

confidence: 99%

“…The spontaneous firing rates and action potential waveforms were similar to those in semi-intact preparations. Specifically, mean firing rates near 20 Hz, as well as interspike trough potentials 20 -30 mV positive to E K , have been reported in acute slices, slice cultures, and brainstem-cerebellar preparations (Jahnsen, 1986a,b;Llinás and Mühlethaler, 1988;Mouginot and Gähwiler, 1995;Aizenman and Linden, 1999). These similarities suggest that the basic pacemaking mechanism may be conserved in the isolated cell preparation, although specific differences in the firing properties of isolated and intact cells are discussed below.…”

Section: Action Potentials Of Isolated Cerebellar Nuclear Neuronsmentioning

confidence: 91%

“…Neurons of the cerebellar nuclei are spontaneously active in semi-intact preparations and fire regularly in resting animals in vivo (Thach, 1968;Jahnsen, 1986a;McDevitt et al, 1987;Llinás and Mühlethaler, 1988;Mouginot and Gähwiler, 1995;Czubayko et al, 1998;Aizenman and Linden, 1999). To our knowledge, however, no voltage-clamp studies have been published of the intrinsic currents that produce the firing patterns of these neurons.…”

Section: Abstract: Deep Cerebellar Nuclei; Pacemaking; Action Potentmentioning

confidence: 99%

“…Additionally, components of TTX-sensitive sodium current that are less susceptible to inactivation appear to drive spontaneous action potentials in several cell types (Pennartz et al, 1997;Feigenspan et al, 1998;Bevan and Wilson, 1999;Raman and Bean, 1999). Furthermore, current-clamp studies have led to the suggestion that cerebellar nuclear neurons have a TTX-sensitive persistent sodium conductance that facilitates repetitive firing (Jahnsen, 1986a;Llinás and Mühlethaler, 1988). Such a current also might lead some cells to rest near Ϫ35 mV.…”

Section: Ttx-sensitive Sodium Currentsmentioning

confidence: 99%

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Ionic Currents and Spontaneous Firing in Neurons Isolated from the Cerebellar Nuclei

2000

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Neurons of the cerebellar nuclei fire spontaneous action potentials both in vitro, with synaptic transmission blocked, and in vivo, in resting animals, despite ongoing inhibition from spontaneously active Purkinje neurons. We have studied the intrinsic currents of cerebellar nuclear neurons isolated from the mouse, with an interest in understanding how these currents generate spontaneous activity in the absence of synaptic input as well as how they allow firing to continue during basal levels of inhibition. Current-clamped isolated neurons fired regularly (ϳ20 Hz), with shallow interspike hyperpolarizations (approximately Ϫ60 mV), much like neurons in more intact preparations. The spontaneous firing frequency lay in the middle of the dynamic range of the neurons and could be modulated up or down with small current injections.During step or action potential waveform voltage-clamp commands, the primary current active at interspike potentials was a tetrodotoxin-insensitive (TTX), cesium-insensitive, voltageindependent, cationic flux carried mainly by sodium ions. Although small, this cation current could depolarize neurons above threshold voltages. Voltage-and current-clamp recordings suggested a high level of inactivation of the TTX-sensitive transient sodium currents that supported action potentials. Blocking calcium currents terminated firing by preventing repolarization to normal interspike potentials, suggesting a significant role for K(Ca) currents. Potassium currents that flowed during action potential waveform voltage commands had high activation thresholds and were sensitive to 1 mM TEA. We propose that, after the decay of high-threshold potassium currents, the tonic cation current contributes strongly to the depolarization of neurons above threshold, thus maintaining the cycle of firing.

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Organization of projections from the inferior olive to the cerebellar nuclei in the rat

2000

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The detailed organization of projections from the inferior olive to the cerebellar nuclei of the rat was studied by using anterograde tracing. The presence of a collateral projection to the cerebellar nuclei could be confirmed, and a detailed organization was recognized at the nuclear and subnuclear level. Olivary projections to the different parts of the medial cerebellar nucleus arise from various parts of the caudal half of the medial accessory olivary nucleus. The interstitial cell groups receive olivary afferents from the intermediate part of the medial accessory olive and from the dorsomedial cell column. A mediolateral topography was noted in the projections from the rostral half of the medial accessory olive to the posterior interposed nucleus. Olivary projections to the lateral cerebellar nucleus are derived from the principal olive according to basically inversed rostrocaudal topography. Projections from the dorsomedial group of the principal olive to the dorsolateral hump were found to follow a basically rostrocaudal topography. The anterior interposed nucleus receives olivary afferents from the dorsal accessory olive. Its rostromedial parts are directed to the lateral part of the anterior interposed nucleus and its caudolateral part reach the medial anterior interposed nucleus. No terminal arborizations in the cerebellar nuclei were found to originate from (1) the dorsal fold of the dorsal accessory olive, which resulted in projections to the lateral vestibular nucleus and (2) the dorsal cap of Kooy. It was noted that the olivary projection to the cerebellar nuclei is strictly reciprocal to the nucleo-olivary projection as described by Ruigrok and Voogd (1990). Moreover, it is suggested that the olivonuclear projection adheres to the organization of the climbing fiber projection to the cerebellar cortex and to the corticonuclear projection, thus, establishing and extending the detailed micromodular organization of the connections between inferior olive and cerebellum.

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Electrophysiology of guinea‐pig cerebellar nuclear cells in the in vitro brain stem‐cerebellar preparation.

Cited by 352 publications

References 31 publications

Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states

Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states

Ionic Currents and Spontaneous Firing in Neurons Isolated from the Cerebellar Nuclei

Organization of projections from the inferior olive to the cerebellar nuclei in the rat

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