Mechanisms of Spontaneous Climbing Fiber Discharge-Evoked Pauses and Output Modulation of Cerebellar Purkinje Cell in Mice

Jin, Xian; Wang, Hong Wei; Zhang, Xin Yuan; Chu, Chun Ping; Jin, Yuan; Cui, Song Biao; Qiu, De Lai

doi:10.3389/fncel.2017.00247

Cited by 10 publications

(6 citation statements)

References 66 publications

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“…3 C, D ) PCs in 12 months old mice. This reciprocal firing is typical for cerebellar PCs (22, 28) and similar reciprocal response was previously observed for the electrical stimulation of the inferior olive (21, 29). With some delay, the restoration of simple spikes generation was registered as a result of harmaline washout (Fig.…”

Section: Resultssupporting

confidence: 85%

In Vivo Analysis of the Climbing Fiber-Purkinje Cell Circuit in SCA2-58Q Transgenic Mouse Model

2018

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Cerebellar Purkinje cells (PCs) and cerebellar pathways are primarily affected in many autosomal dominant cerebellar ataxias. PCs generate complex spikes (CS) in vivo when activated by climbing fiber (CF) which rise from the inferior olive. In this study, we investigated the functional state of the CF-PC circuitry in the transgenic mouse model of spinocerebellar ataxia type 2 (SCA2), a polyglutamine neurodegenerative genetic disease. In our experiments, we used an extracellular single-unit recording method to compare the PC activity pattern and the CS shape in age-matched wild-type mice and SCA2-58Q transgenic mice. We discovered no alterations in the CS properties of PCs in aging SCA2 mice. To examine the integrity of the olivocerebellar pathway, we applied harmaline, an alkaloid that acts directly on the inferior olive neurons. The pharmacological stimulation of olivocerebellar circuit by harmaline uncovered disturbances in SCA2-58Q PC activity pattern and in the complex spike shape when compared with age-matched wild-type cells. The abnormalities in the CF-PC circuitry were aggravated with age. We propose that alterations in CF-PC circuitry represent one of potential causes of ataxic symptoms in SCA2 and in other SCAs.

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Section: Resultssupporting

confidence: 85%

In Vivo Analysis of the Climbing Fiber-Purkinje Cell Circuit in SCA2-58Q Transgenic Mouse Model

2018

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“…SK channels have an impact on the setting intrinsic firing frequency [ 90 ] whereas BK channels are involved in the regulation of AP waveform and presumably climbing fiber responses [ 68 91 ]. Recent studies have shown that CF-evoked pause of spontaneous firing and generation of burst firing in PCs require BK channels coupled to Ca 2+ channels [ 92 93 ]. Because SK and BK channels in PCs play a critical role in the regulation of firing behavior, dysfunction of these channels has been implicated in cerebellar disease such as ataxia.…”

Section: Ion Channels and Spiking Activity Of The Cerebellar Pcsmentioning

confidence: 99%

The Emerging Concept of Intrinsic Plasticity: Activity-dependent Modulation of Intrinsic Excitability in Cerebellar Purkinje Cells and Motor Learning

2018

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What is memory? How does the brain process the sensory information and modify an organism's behavior? Many neuroscientists have focused on the activity- and experience-dependent modifications of synaptic functions in order to solve these fundamental questions in neuroscience. Recently, the plasticity of intrinsic excitability (called intrinsic plasticity) has emerged as an important element for information processing and storage in the brain. As the cerebellar Purkinje cells are the sole output neurons in the cerebellar cortex and the information is conveyed from a neuron to its relay neurons by forms of action potential firing, the modulation of the intrinsic firing activity may play a critical role in the cerebellar learning. Many voltage-gated and/or Ca2+-activated ion channels are involved in shaping the spiking output as well as integrating synaptic inputs to finely tune the cerebellar output. Recent studies suggested that the modulation of the intrinsic excitability and its plasticity in the cerebellar Purkinje cells might function as an integrator for information processing and memory formation. Moreover, the intrinsic plasticity might also determine the strength of connectivity to the sub-cortical areas such as deep cerebellar nuclei and vestibular nuclei to trigger the consolidation of the cerebellar-dependent memory by transferring the information.

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“…In the absence of complex spiking, simple spike firing frequencies increase to exceptionally high levels (Cerminara and Rawson, 2004). SK channels are also responsible for afterhyperpolarisations that follow bursts of action potentials (Ohtsuki et al, 2012), which may underlie the climbing fibre-induced pause and downregulation of simple spikes (Jin et al, 2017). The model of the calcium-activated potassium current used here and taken from Gillies and Willshaw (2006) is one of a number of models for the SK channel, for example, the alternative model used in Griffith et al (2016) based on Chay and Keizer (1983); Xia et al (1998) has a steeper and quicker modulation of the channel by calcium concentration.…”

Section: Discussionmentioning

confidence: 99%

“…The models presented in this study are tuned to match complex spikes recorded in vitro in Davie et al (2008). This example is chosen because it typifies features of the complex spike waveform observed in numerous in vitro studies (Zagha et al, 2008;Zhang et al, 2017;Monsivais et al, 2005;Khaliq and Raman, 2005) and in an in vivo study, Warnaar et al (2015): in vivo studies that give wave form data are less common. These feature, which are broadly stereotypical are 1. the first spike is similar in shape to the simple spike, 2. the first spikelet is smaller in amplitude than subsequent spikelets, 3. spikelets get further apart with increasing current injections or spikelet number.…”

Section: Discussionmentioning

confidence: 99%

A Purkinje cell model that simulates complex spikes

Burroughs

Cerminara

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et al. 2020

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Purkinje cells are the principal neurons of the cerebellar cortex. One of their distinguishing features is that they fire two distinct types of action potential, called simple and complex spikes, which interact with one another. Simple spikes are stereotypical action potentials that are elicited at high, but variable, rates (0 − 100 Hz) and have a consistent waveform. Complex spikes are composed of an initial action potential followed by a burst of lower amplitude spikelets. Complex spikes occur at comparatively low rates (∼ 1 Hz) and have a variable waveform. Although they are critical to cerebellar operation a simple model that describes the complex spike waveform is lacking. Here, a novel single-compartment model of Purkinje cell electrodynamics is presented. The simpler version of this model, with two active conductances and a leak channel, can simulate the features typical of complex spikes recorded in vitro. If calcium dynamics are also included, the model can capture the pause in simple spike activity that occurs after complex spike events. Together, these models provide an insight into the mechanisms behind complex spike spikelet generation, waveform variability and their interactions with simple spike activity.

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Mechanisms of Spontaneous Climbing Fiber Discharge-Evoked Pauses and Output Modulation of Cerebellar Purkinje Cell in Mice

Cited by 10 publications

References 66 publications

In Vivo Analysis of the Climbing Fiber-Purkinje Cell Circuit in SCA2-58Q Transgenic Mouse Model

In Vivo Analysis of the Climbing Fiber-Purkinje Cell Circuit in SCA2-58Q Transgenic Mouse Model

The Emerging Concept of Intrinsic Plasticity: Activity-dependent Modulation of Intrinsic Excitability in Cerebellar Purkinje Cells and Motor Learning

A Purkinje cell model that simulates complex spikes

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