Computational Reconstruction of Pacemaking and Intrinsic Electroresponsiveness in Cerebellar Golgi Cells

The Golgi cells have been recently shown to beat regularly in vitro (Forti et al., 2006. J. Physiol. 574, 711–729). Four main currents were shown to be involved, namely a persistent sodium current (I Na-p), an h current (I h), an SK-type calcium-dependent potassium current (I K-AHP), and a slow M-like potassium current (I K-slow). These ionic currents could take part, together with others, also to different aspects of neuronal excitability like responses to depolarizing and hyperpolarizing current injection. However, the ionic mechanisms and their interactions remained largely hypothetical. In this work, we have investigated the mechanisms of Golgi cell excitability by developing a computational model. The model predicts that pacemaking is sustained by subthreshold oscillations tightly coupled to spikes. I Na-p and I K-slow emerged as the critical determinants of oscillations. I h also played a role by setting the oscillatory mechanism into the appropriate membrane potential range. I K-AHP, though taking part to the oscillation, appeared primarily involved in regulating the ISI following spikes. The combination with other currents, in particular a resurgent sodium current (I Na-r) and an A-current (I K-A), allowed a precise regulation of response frequency and delay. These results provide a coherent reconstruction of the ionic mechanisms determining Golgi cell intrinsic electroresponsiveness and suggests important implications for cerebellar signal processing, which will be fully developed in a companion paper (Solinas et al., 2008. Front. Neurosci. 2:4).

• Publication year

  2007

• Venue

  Frontiers in Cellular Neuroscience

• Publication date

  2007-09-21

• Fields of study

  Biology, Medicine, Chemistry, Computer Science

• Identifiers
  DOI 10.3389/neuro.03.002.2007PMID 18946520PMCID 2525930
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A Novel Multiple Objective Optimization Framework for Constraining Conductance-Based Neuron Models by Experimental Data

  2007cited by this paper
• Heterogeneity of glycinergic and gabaergic interneurons in the granule cell layer of mouse cerebellum

  2007influential reference
• Regular Patterns in Cerebellar Purkinje Cell Simple Spike Trains

  2007cited by this paper
• Fast-Reset of Pacemaking and Theta-Frequency Resonance Patterns in Cerebellar Golgi Cells: Simulations of their Impact In Vivo

  2007cited by this paper
• Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells

  2006influential reference
• LTP regulates burst initiation and frequency at mossy fiber-granule cell synapses of rat cerebellum: experimental observations and theoretical predictions.

  2006influential reference
• Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study

  2006influential reference
• Complex Parameter Landscape for a Complex Neuron Model

  2006influential reference
• Temporal characteristics of tactile stimuli influence the response profile of cerebellar Golgi cells.

  2005cited by this paper
• Autonomous pacemakers in the basal ganglia: who needs excitatory synapses anyway?

  2005influential reference
• SK channels in excitability, pacemaking and synaptic integration.

  2005cited by this paper
• Resurgent Na currents in four classes of neurons of the cerebellum.

  2004influential reference
• HCN2 and HCN1 Channels Govern the Regularity of Autonomous Pacemaking and Synaptic Resetting in Globus Pallidus Neurons

  2004cited by this paper
• Ca2+-activated K+ channels: molecular determinants and function of the SK family

  2004influential reference
• Apamin-Sensitive Small Conductance Calcium-Activated Potassium Channels, through their Selective Coupling to Voltage-Gated Calcium Channels, Are Critical Determinants of the Precision, Pace, and Pattern of Action Potential Generation in Rat Subthalamic Nucleus Neurons In Vitro

  2003cited by this paper
• Theta-Frequency Bursting and Resonance in Cerebellar Granule Cells: Experimental Evidence and Modeling of a Slow K+-Dependent Mechanism

  2001influential reference
• Biophysics of Computation

  2001influential reference
• Activation of Expressed KCNQ Potassium Currents and Native Neuronal M-Type Potassium Currents by the Anti-Convulsant Drug Retigabine

  2001influential reference
• Neuron: A Tool for Neuroscientists

  2001influential reference
• Compartmental models of rat cerebellar Purkinje cells based on simultaneous somatic and dendritic patch‐clamp recordings

  2001influential reference
• Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum.

  2001influential reference
• Properties and role of I(h) in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons.

  2000influential reference
• Differential distribution of three Ca(2+)-activated K(+) channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system.

  2000cited by this paper
• Oscillatory Activity in Entorhinal Neurons and Circuits: Mechanisms and Function

  2000cited by this paper
• Intrinsic Membrane Properties Underlying Spontaneous Tonic Firing in Neostriatal Cholinergic Interneurons

  2000influential reference
• Molecular and Functional Heterogeneity of Hyperpolarization-Activated Pacemaker Channels in the Mouse CNS

  2000cited by this paper
• Coupled oscillator model of the dopaminergic neuron of the substantia nigra.

  2000cited by this paper
• Resonance, oscillation and the intrinsic frequency preferences of neurons.

  2000cited by this paper
• A Comparative Survey of Automated Parameter-Search Methods for Compartmental Neural Models

  1999influential reference
• Mechanisms Underlying Spontaneous Oscillation and Rhythmic Firing in Rat Subthalamic Neurons

  1999cited by this paper
• Properties of a Neuronal and Network Pacemaker

  1998cited by this paper
• Calcium dynamics in large neuronal models

  1998influential reference
• Ionic mechanisms of intrinsic oscillations in neurons of the basolateral amygdaloid complex.

  1998cited by this paper
• Gating of Recombinant Small-Conductance Ca-activated K+ Channels by Calcium

  1998cited by this paper
• H-current: properties of a neuronal and network pacemaker.

  1998cited by this paper
• Synchronization of golgi and granule cell firing in a detailed network model of the cerebellar granule cell layer.

  1998cited by this paper
• Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons

  1998cited by this paper
• Single‐Channel Recording

  1998cited by this paper
• Submillisecond kinetics and low efficacy of parallel fibre‐Golgi cell synaptic currents in the rat cerebellum

  1998influential reference
• Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons

  1997cited by this paper
• Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: involvement of a slowly inactivating component of sodium current.

  1997cited by this paper
• The Role of Synaptic and Voltage-Gated Currents in the Control of Purkinje Cell Spiking: A Modeling Study

  1997cited by this paper
• Single-Channel Recording

  1995cited by this paper
• Subthreshold oscillations and resonant frequency in guinea‐pig cortical neurons: physiology and modelling.

  1995influential reference
• A model of spindle rhythmicity in the isolated thalamic reticular nucleus.

  1994cited by this paper
• Synaptic integration in a model of cerebellar granule cells.

  1994cited by this paper
• An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses.

  1994cited by this paper
• A model of the electrophysiological properties of thalamocortical relay neurons.

  1992influential reference
• Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons.

  1992cited by this paper
• A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances.

  1991influential reference
• Noradrenergic and serotonergic modulation of a hyperpolarization‐activated cation current in thalamic relay neurones.

  1990influential reference
• Subthreshold Na+-dependent theta-like rhythmicity in stellate cells of entorhinal cortex layer II

  1989cited by this paper
• Multiple channels and calcium dynamics

  1989influential reference
• The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function.

  1988cited by this paper
• Oscillatory properties of guinea‐pig inferior olivary neurones and their pharmacological modulation: an in vitro study.

  1986cited by this paper
• Simulation of intrinsic bursting in CA3 hippocampal neurons.

  1982influential reference
• Long-term adaptive changes in primate vestibuloocular reflex. III. Electrophysiological observations in flocculus of normal monkeys.

  1980cited by this paper
• Long-term adaptive changes in primate vestibuloocular reflex. I. Behavioral observations.

  1980cited by this paper
• Hippocampal pyramidal cells: significance of dendritic ionic conductances for neuronal function and epileptogenesis.

  1979influential reference
• A theory of cerebellar cortex

  1969cited by this paper
• The Cerebellum as a Neuronal Machine

  1967cited by this paper
• A quantitative description of membrane current and its application to conduction and excitation in nerve

  1952influential reference

• Exploring the Mechanisms of Bidirectional Plasticity From Temporal Feature Stimuli in Cerebellar Motor Learning: A Ca2+-Mediated Simulation

  2025cites this paper
• The Long Journey from Animal Electricity to the Discovery of Ion Channels and the Modelling of the Human Brain

  2024cites this paper
• Ion-channel degeneracy and heterogeneities in the emergence of signature physiological characteristics of dentate gyrus granule cells

  2024cites this paper
• A Reinterpretation of the Relationship between Persistent and Resurgent Sodium Currents

  2024cites this paper
• Advancements in Cerebellar Modeling and Its Practical Applications: A Comprehensive Review

  2024influential citation
• The NeuroML ecosystem for standardized multi-scale modeling in neuroscience

  2024cites this paper
• A biophysically comprehensive model of urothelial afferent neurons: implications for sensory signalling in urinary bladder

  2024cites this paper
• Purkinje cell models: past, present and future

  2024cites this paper
• Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity

  2023cites this paper
• A multi-layer mean-field model of the cerebellum embedding microstructure and population-specific dynamics

  2023cites this paper
• A Reinterpretation of the Relationship Between Persistent and Resurgent Sodium Currents

  2023cites this paper
• Long-Term Synaptic Plasticity Tunes the Gain of Information Channels through the Cerebellum Granular Layer

  2022cites this paper
• Computational models of neurotransmission at cerebellar synapses unveil the impact on network computation

  2022cites this paper
• A multi-layer mean-field model for the cerebellar cortex: design, validation, and prediction

  2022influential citation
• Modeling Neurotransmission: Computational Tools to Investigate Neurological Disorders

  2021cites this paper
• Multidimensional population activity in an electrically coupled inhibitory circuit in the cerebellar cortex

  2021cites this paper
• Testing an Explicit Method for Multi-compartment Neuron Model Simulation on a GPU

  2021cites this paper
• Real-Time Simulation of a Cerebellar Scaffold Model on Graphics Processing Units

  2021cites this paper
• Human-scale brain simulation via supercomputer: a case study on the cerebellum.

  2021cites this paper
• Stellate cell computational modeling predicts signal filtering in the molecular layer circuit of cerebellum

  2021cites this paper
• Granular layEr Simulator: Design and Multi-GPU Simulation of the Cerebellar Granular Layer

  2021cites this paper
• NeuroML-DB: Sharing and characterizing data-driven neuroscience models described in NeuroML

  2021cites this paper
• Cerebellar Nuclei and Cerebellar Learning

  2021cites this paper
• Pycabnn: Efficient and Extensible Software to Construct an Anatomical Basis for a Physiologically Realistic Neural Network Model

  2020cites this paper
• Chaos may enhance expressivity in cerebellar granular layer

  2020cites this paper
• Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity

  2020influential citation
• Cellular-resolution mapping uncovers spatial adaptive filtering at the cerebellum input stage

  2020cites this paper
• Cellular-resolution mapping uncovers spatial adaptive filtering at the rat cerebellum input stage

  2020cites this paper
• Molecular layer interneurons in the cerebellum encode for valence in associative learning

  2019cites this paper
• Using cerebellar Purkinje cell models at different levels of abstraction as a read-out mechanism for pattern recognition in a biologically detailed granular layer model

  2019cites this paper
• Exploiting multi-core and many-core architectures for efficient simulation of biologically realistic models of Golgi cells

  2019cites this paper
• Two Distinct Sets of Ca2+ and K+ Channels Are Activated at Different Membrane Potentials by the Climbing Fiber Synaptic Potential in Purkinje Neuron Dendrites

  2019cites this paper
• Reconstruction and Simulation of a Scaffold Model of the Cerebellar Network

  2019cites this paper
• Complex Electroresponsive Dynamics in Olivocerebellar Neurons Represented With Extended-Generalized Leaky Integrate and Fire Models

  2019cites this paper
• Diverse Neuron Properties and Complex Network Dynamics in the Cerebellar Cortical Inhibitory Circuit

  2019cites this paper
• Hardware Implementation of the Cerebellar Neural Network with Conductance-based Models

  2018cites this paper
• Cerebellum and its Disorders

  2018cites this paper
• Open Source Brain: A Collaborative Resource for Visualizing, Analyzing, Simulating, and Developing Standardized Models of Neurons and Circuits

  2018cites this paper
• Complex Dynamics in Simplified Neuronal Models: Reproducing Golgi Cell Electroresponsiveness

  2018cites this paper
• Physiology of the cerebellum.

  2018cites this paper
• Voltage- and Branch-specific Climbing Fiber Responses in Purkinje Cells

  2018cites this paper
• Understanding Cerebellum Granular Layer Network Computations through Mathematical Reconstructions of Evoked Local Field Potentials

  2017cites this paper
• High Performant Simulations of Cerebellar Golgi Cells Activity

  2017cites this paper
• Single Neuron Optimization as a Basis for Accurate Biophysical Modeling: The Case of Cerebellar Granule Cells

  2017influential citation
• T2N as a new tool for robust electrophysiological modeling demonstrated for mature and adult-born dentate granule cells

  2017influential citation
• Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity

  2017cites this paper
• Computational Neuroscience of Timing, Plasticity and Function in Cerebellum Microcircuits

  2017cites this paper
• Computational characterization of cerebellum granule neuron responses to auditory and visual inputs

  2016cites this paper
• Single-Neuron and Network Computation in Realistic Models of the Cerebellar Cortex

  2016cites this paper
• Computational Modeling of Single Neuron Extracellular Electric Potentials and Network Local Field Potentials using LFPsim

  2016cites this paper
• Challenging Marr’s theory of the cerebellum

  2016cites this paper
• Computing LFP from biophysical models of neurons and neural microcircuits

  2016cites this paper
• Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

  2016cites this paper
• Models of the cortico-cerebellar system

  2016cites this paper
• Exploiting point source approximation on detailed neuronal models to reconstruct single neuron electric field and population LFP

  2015cites this paper
• Computational Modeling of Neuronal Dysfunction at Molecular Level Validates the Role of Single Neurons in Circuit Functions in Cerebellum Granular Layer

  2015cites this paper
• High frequency field potentials of the cerebellar cortex

  2015cites this paper
• Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

  2015cites this paper
• High frequency synchrony in the cerebellar cortex during goal directed movements

  2015cites this paper
• Single Granule Cells Excite Golgi Cells and Evoke Feedback Inhibition in the Cochlear Nucleus

  2015influential citation
• Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation

  2015cites this paper
• Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells

  2014cites this paper
• Computationally EfficientBio-realistic Reconstructions of Cerebellar Neuron Spiking Patterns

  2014cites this paper
• Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

  2014cites this paper
• Parallelization of a Computational Model of a Biophysical Neuronal Circuitry of Rat Cerebellum

  2014cites this paper
• Dendritic diameters affect the spatial variability of intracellular calcium dynamics in computer models

  2014cites this paper
• Integration and regulation of glomerular inhibition in the cerebellar granular layer circuit

  2014cites this paper
• GPGPU Implementation of a Spiking Neuronal Circuit Performing Sparse Recoding

  2014cites this paper
• Regulation of output spike patterns by phasic inhibition in cerebellar granule cells

  2014influential citation
• NeuVision: A novel simulation environment to model spontaneous and stimulus-evoked activity of large-scale neuronal networks

  2013cites this paper
• Theta-Frequency Resonance at the Cerebellum Input Stage Improves Spike Timing on the Millisecond Time-Scale

  2013cites this paper
• Late‐onset bursts evoked by mossy fibre bundle stimulation in unipolar brush cells: evidence for the involvement of H‐ and TRP‐currents

  2013cites this paper
• Bistability in Purkinje neurons: Ups and downs in cerebellar research

  2013cites this paper
• Gap junctions and neuronal synchronization in the olivocerebellar system.

  2013cites this paper
• Event time representation in cerebellar mossy fibres arising from the lateral reticular nucleus

  2013cites this paper
• The Golgi cell relationship between these several and diverse activities and what is the exact role of Golgi cells in cerebellar computation ? FUNDAMENTAL PROPERTIES OF GOLGI CELLS

  2013cites this paper
• Spike Timing Regulation on the Millisecond Scale by Distributed Synaptic Plasticity at the Cerebellum Input Stage: A Simulation Study

  2013cites this paper
• Na+/K+-ATPase Inhibition Partially Mimics the Ethanol-Induced Increase of the Golgi Cell-Dependent Component of the Tonic GABAergic Current in Rat Cerebellar Granule Cells

  2013cites this paper
• Stochastic Calcium Mechanisms Cause Dendritic Calcium Spike Variability

  2013cites this paper
• Realistic modeling of neurons and networks: towards brain simulation.

  2013cites this paper
• The cerebellar Golgi cell and spatiotemporal organization of granular layer activity

  2013cites this paper
• After-hyperpolarization currents and acetylcholine control sigmoid transfer functions in a spiking cortical model

  2012cites this paper
• Modeling Spike-Train Processing in the Cerebellum Granular Layer and Changes in Plasticity Reveal Single Neuron Effects in Neural Ensembles

  2012influential citation
• The Generation of Phase Differences and Frequency Changes in a Network Model of Inferior Olive Subthreshold Oscillations

  2012cites this paper
• Excitation of rat cerebellar Golgi cells by ethanol: further characterization of the mechanism.

  2012cites this paper
• Gap Junctions Compensate for Sublinear Dendritic Integration in an Inhibitory Network

  2012cites this paper
• Simulation of biological neuronal structures. Design and functional study of the cerebellum

  2012influential citation
• New tools and specification languages for biophysically detailed neuronal network modelling

  2012cites this paper
• A computational study on the spatial correlation of granule cell firing in the cerebellar cortex

  2012cites this paper
• Local Field Potential Modeling Predicts Dense Activation in Cerebellar Granule Cells Clusters under LTP and LTD Control

  2011cites this paper
• Sensory Coding by Cerebellar Mossy Fibres through Inhibition-Driven Phase Resetting and Synchronisation

  2011cites this paper
• Role of Calcium in Cerebellar Learning and Function

  2011cites this paper
• Robustness effect of gap junctions between Golgi cells on cerebellar cortex oscillations

  2011cites this paper
• Neural circuits of the cerebellum: hypothesis for function.

  2011cites this paper
• The cerebellar network: from structure to function and dynamics.

  2011cites this paper
• Realistic Modeling of Large-Scale Networks: Spatio-temporal Dynamics and Long-Term Synaptic Plasticity in the Cerebellum

  2011cites this paper
• Neural circuit and its functional roles in cerebellar cortex

  2011cites this paper
• NeuroML: A Language for Describing Data Driven Models of Neurons and Networks with a High Degree of Biological Detail

  2010cites this paper
• Modeling spatio-temporal processing in cerebellar granular layer and effects of controlled inhibition on plasticity

  2010cites this paper
• Realistic circuit modeling: large-scale simulations of the cerebellar granular layer

  2010cites this paper