SK2 Channel Modulation Contributes to Compartment-Specific Dendritic Plasticity in Cerebellar Purkinje Cells

Ohtsuki, Gen; Piochon, Claire; Adelman, John P.; Hansel, Christian

doi:10.1016/j.neuron.2012.05.025

Cited by 102 publications

(159 citation statements)

References 58 publications

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“…when potentiated synapses receive further intrinsic amplification. This phenomenon has been observed in layer 5 pyramidal neurons of the sensorimotor cortex (Sourdet et al, 2003) as well as in cerebellar Purkinje cells (Ohtsuki et al, 2012). Here, we focused on SK channel plasticity as an example to describe various consequences of intrinsic plasticity, because SK channel modulation has been particularly well studied.…”

Section: Intrinsic Plasticity: Cellular Mechanisms and Relevance To Lmentioning

confidence: 84%

Toward a Neurocentric View of Learning

Titley

Brunel

Hansel

2017

Neuron

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184

177

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Synaptic plasticity (e.g. long-term potentiation; LTP) is considered as the cellular correlate of learning. Recent optogenetic studies on memory engram formation assign a critical role in learning to suprathreshold activation of neurons and their integration into active engrams (‘engram cells’). Here we review evidence that ensemble integration may result from LTP, but also from cell-autonomous changes in membrane excitability. We propose that synaptic plasticity determines synaptic connectivity maps, while intrinsic plasticity – possibly separated in time – amplifies neuronal responsiveness and acutely drives engram integration. Our proposal marks a move away from an exclusively synaptocentric toward a non-exclusive, neurocentric view of learning.

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Section: Intrinsic Plasticity: Cellular Mechanisms and Relevance To Lmentioning

confidence: 84%

Toward a Neurocentric View of Learning

Titley

Brunel

Hansel

2017

Neuron

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184

177

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“…We recently identified a functional SK2 channel splice variant, SK2-b, which is less sensitive to Ca 2+ for its activation (14). By dampening the firing of action potentials, activation of SK/IK channels contributes to the regulation of neuronal excitability, dendritic integration, synaptic transmission, and plasticity in the central nervous system (9,11,13,15,16). In the cardiovascular system, vascular endothelial cells express both IK and SK3 channels, which are implicated in the endothelium-derived hyperpolarizing factor-mediated vasodilation (17)(18)(19)(20).…”

Section: +mentioning

confidence: 99%

Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca ²⁺ -sensing and SK channel activation

Zhang¹,

Pascal²,

Zhang

2013

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

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Most proteins, such as ion channels, form well-organized 3D structures to carry out their specific functions. A typical voltagegated potassium channel subunit has six transmembrane segments (S1-S6) to form the voltage-sensing domain and the pore domain. Conformational changes of these domains result in opening of the channel pore. Intrinsically disordered (ID) proteins/peptides are considered equally important for the protein functions. However, it is difficult to explore the structural features underlying the functions of ID proteins/peptides by conventional methods, such as X-ray crystallography, because of the flexibility of their secondary structures. Unlike voltage-gated potassium channels, families of small-and intermediate-conductance Ca 2+ -activated potassium (SK/IK) channels with important roles in regulating membrane excitability are activated exclusively by Ca 2+ -bound calmodulin (CaM). Upon binding of Ca 2+ to CaM, a 2 × 2 structure forms between CaM and the CaMbinding domain. A channel fragment that connects S6 and the CaMbinding domain is not visible in the protein crystal structure, suggesting that this fragment is an ID fragment. Here we show that the conformation of the ID fragment in SK channels becomes readily identifiable in the presence of NS309, the most potent compound that potentiates the channel activities. This well-defined conformation of the ID fragment, stabilized by NS309, increases the channel open probability at a given Ca 2+ concentration. Our results demonstrate that the ID fragment, itself a target for drugs modulating SK channel activities, plays a unique role in coupling Ca 2+ sensing by CaM and mechanical opening of SK channels.calcium | signaling | gating M ost proteins typically adopt one or more well-defined 3D structures, or domains, to carry out their specific functions. Voltage-gated potassium channels are such an example, with six transmembrane segments (S1-S6) forming the voltage-sensing domain and the pore domain (1, 2). Conformational changes of these domains result in opening of the channel pore. Unlike the well-structured proteins, there are proteins or fragments of proteins that lack well-defined 3D conformations (3-8). These proteins, termed "intrinsically disordered" (ID) proteins/peptides, typically are flexible in their secondary structures and often can adopt multiple conformations. Consequently, the structures of ID proteins are difficult to determine by conventional methods, such as X-ray crystallography, and it is difficult to explore the structural features responsible for functions by ID proteins. Nevertheless, emerging evidence shows that ID proteins/peptides are equally important for the protein functions.Small-and intermediate-conductance Ca 2+

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“…Cerebellar Purkinje cells provide an interesting case to study consequences of intrinsic modulation for the generation of characteristic spike patterns, because activity-dependent intrinsic plasticity has been observed in these neurons in vitro and in vivo (Schreurs et al, 1998; Belmeguenai et al, 2010; Ohtsuki et al, 2012). Moreover, changes in Purkinje cell excitability have been described subsequent to motor learning (Schreurs et al, 1998), pointing toward a possible causal relationship between altered intrinsic excitability and learning.…”

Section: Introductionmentioning

confidence: 99%

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

Grasselli

Wan

et al. 2016

Cell Reports

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Summary Plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst–pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice) and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.

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SK2 Channel Modulation Contributes to Compartment-Specific Dendritic Plasticity in Cerebellar Purkinje Cells

Cited by 102 publications

References 58 publications

Toward a Neurocentric View of Learning

Toward a Neurocentric View of Learning

Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca ²⁺ -sensing and SK channel activation

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

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SK2 Channel Modulation Contributes to Compartment-Specific Dendritic Plasticity in Cerebellar Purkinje Cells

Cited by 102 publications

References 58 publications

Toward a Neurocentric View of Learning

Toward a Neurocentric View of Learning

Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca 2+ -sensing and SK channel activation

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

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Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca ²⁺ -sensing and SK channel activation