Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells

Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF)-to-Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinase A (PKA) and casein kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei, but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, nonpotentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output.

[1]  J. Byrne,et al.  More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory , 2010, Trends in Neurosciences.

[2]  J. Disterhoft,et al.  Learning-related postburst afterhyperpolarization reduction in CA1 pyramidal neurons is mediated by protein kinase A , 2009, Proceedings of the National Academy of Sciences.

[3]  D. Johnston,et al.  Kinase‐dependent modification of dendritic excitability after long‐term potentiation , 2009, The Journal of physiology.

[4]  Adam Kohn,et al.  Questioning the role of rebound firing in the cerebellum , 2008, Nature Neuroscience.

[5]  Masahiko Watanabe,et al.  SK2 channel plasticity contributes to LTP at Schaffer collateral–CA1 synapses , 2008, Nature Neuroscience.

[6]  Daniel Johnston,et al.  Plasticity of Intrinsic Excitability during Long-Term Depression Is Mediated through mGluR-Dependent Changes in Ih in Hippocampal CA1 Pyramidal Neurons , 2007, The Journal of Neuroscience.

[7]  C. Levenes,et al.  NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell , 2007, The Journal of Neuroscience.

[8]  Michael London,et al.  Local and Global Effects of Ih Distribution in Dendrites of Mammalian Neurons , 2007, The Journal of Neuroscience.

[9]  H. Jörntell,et al.  Ketamine and xylazine depress sensory-evoked parallel fiber and climbing fiber responses. , 2007, Journal of neurophysiology.

[10]  Michael Häusser,et al.  Linking Synaptic Plasticity and Spike Output at Excitatory and Inhibitory Synapses onto Cerebellar Purkinje Cells , 2007, The Journal of Neuroscience.

[11]  W Hamish Mehaffey,et al.  Climbing fiber discharge regulates cerebellar functions by controlling the intrinsic characteristics of purkinje cell output. , 2007, Journal of neurophysiology.

[12]  B. Fakler,et al.  Organization and Regulation of Small Conductance Ca2+-activated K+ Channel Multiprotein Complexes , 2007, The Journal of Neuroscience.

[13]  Kamran Khodakhah,et al.  The Linear Computational Algorithm of Cerebellar Purkinje Cells , 2006, The Journal of Neuroscience.

[14]  Daniel Johnston,et al.  Deletion of Kv4.2 Gene Eliminates Dendritic A-Type K+ Current and Enhances Induction of Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons , 2006, The Journal of Neuroscience.

[15]  Henrik Jörntell,et al.  Properties of Somatosensory Synaptic Integration in Cerebellar Granule Cells In Vivo , 2006, The Journal of Neuroscience.

[16]  Henrik Jörntell,et al.  Synaptic Memories Upside Down: Bidirectional Plasticity at Cerebellar Parallel Fiber-Purkinje Cell Synapses , 2006, Neuron.

[17]  Chris I. De Zeeuw,et al.  αCaMKII Is Essential for Cerebellar LTD and Motor Learning , 2006, Neuron.

[18]  R. Stackman,et al.  Small-Conductance Ca2+-Activated K+ Channel Type 2 (SK2) Modulates Hippocampal Learning, Memory, and Synaptic Plasticity , 2006, The Journal of Neuroscience.

[19]  Michael Häusser,et al.  Dendritic Calcium Spikes Are Tunable Triggers of Cannabinoid Release and Short-Term Synaptic Plasticity in Cerebellar Purkinje Neurons , 2006, The Journal of Neuroscience.

[20]  J. Adelman,et al.  Regulation of Surface Localization of the Small Conductance Ca2+-activated Potassium Channel, Sk2, through Direct Phosphorylation by cAMP-dependent Protein Kinase* , 2006, Journal of Biological Chemistry.

[21]  Kamran Khodakhah,et al.  Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia , 2006, Nature Neuroscience.

[22]  C. Hansel,et al.  A Role for Protein Phosphatases 1, 2A, and 2B in Cerebellar Long-Term Potentiation , 2005, The Journal of Neuroscience.

[23]  R. Chitwood,et al.  Activity-dependent decrease of excitability in rat hippocampal neurons through increases in Ih , 2005, Nature Neuroscience.

[24]  Spencer L. Smith,et al.  Pattern-dependent, simultaneous plasticity differentially transforms the input-output relationship of a feedforward circuit. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  D. Johnston,et al.  Plasticity of dendritic excitability. , 2005, Journal of neurobiology.

[26]  Aryn H. Gittis,et al.  Decreases in CaMKII Activity Trigger Persistent Potentiation of Intrinsic Excitability in Spontaneously Firing Vestibular Nucleus Neurons , 2005, Neuron.

[27]  B. Sabatini,et al.  SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines , 2005, Nature Neuroscience.

[28]  C. Hansel,et al.  Bidirectional Parallel Fiber Plasticity in the Cerebellum under Climbing Fiber Control , 2004, Neuron.

[29]  M. Mann,et al.  Protein Kinase CK2 Is Coassembled with Small Conductance Ca2+-Activated K+ Channels and Regulates Channel Gating , 2004, Neuron.

[30]  Robert H. Cudmore,et al.  Long-term potentiation of intrinsic excitability in LV visual cortical neurons. , 2004, Journal of neurophysiology.

[31]  J. Marksteiner,et al.  Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain , 2004, Molecular and Cellular Neuroscience.

[32]  J F Storm,et al.  Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+-activated K+ channel deficiency. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  M. Häusser,et al.  Integration of quanta in cerebellar granule cells during sensory processing , 2004, Nature.

[34]  Daniel Johnston,et al.  LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites , 2004, Nature Neuroscience.

[35]  Matthew F. Nolan,et al.  The Hyperpolarization-Activated HCN1 Channel Is Important for Motor Learning and Neuronal Integration by Cerebellar Purkinje Cells , 2003, Cell.

[36]  Dominique Debanne,et al.  Long-Term Enhancement of Neuronal Excitability and Temporal Fidelity Mediated by Metabotropic Glutamate Receptor Subtype 5 , 2003, The Journal of Neuroscience.

[37]  D. Linden,et al.  The other side of the engram: experience-driven changes in neuronal intrinsic excitability , 2003, Nature Reviews Neuroscience.

[38]  Kamran Khodakhah,et al.  Somatic and Dendritic Small-Conductance Calcium-Activated Potassium Channels Regulate the Output of Cerebellar Purkinje Neurons , 2003, The Journal of Neuroscience.

[39]  J. Edgerton,et al.  Distinct contributions of small and large conductance Ca2+‐activated K+ channels to rat Purkinje neuron function , 2003, The Journal of physiology.

[40]  Mu-ming Poo,et al.  Bidirectional Changes in Spatial Dendritic Integration Accompanying Long-Term Synaptic Modifications , 2003, Neuron.

[41]  Cornelius Schwarz,et al.  Efficacy and short-term plasticity at GABAergic synapses between Purkinje and cerebellar nuclei neurons. , 2003, Journal of neurophysiology.

[42]  Thanos Tzounopoulos,et al.  Small Conductance Ca2+-Activated K+Channels Modulate Synaptic Plasticity and Memory Encoding , 2002, The Journal of Neuroscience.

[43]  Karl Peter Giese,et al.  Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning , 2002, Neuron.

[44]  Dominique Debanne,et al.  Bidirectional plasticity of excitatory postsynaptic potential (EPSP)-spike coupling in CA1 hippocampal pyramidal neurons , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[45]  I. Raman,et al.  Depression of Inhibitory Synaptic Transmission between Purkinje Cells and Neurons of the Cerebellar Nuclei , 2002, The Journal of Neuroscience.

[46]  J. Storm,et al.  A postsynaptic transient K+ current modulated by arachidonic acid regulates synaptic integration and threshold for LTP induction in hippocampal pyramidal cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[47]  B. Sakmann,et al.  In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain , 2002, Pflügers Archiv.

[48]  Roger Y Tsien,et al.  A new form of cerebellar long-term potentiation is postsynaptic and depends on nitric oxide but not cAMP , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Shigeo Watanabe,et al.  Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[50]  P. Pedarzani,et al.  Developmental Regulation of Small-Conductance Ca2+-Activated K+ Channel Expression and Function in Rat Purkinje Neurons , 2002, The Journal of Neuroscience.

[51]  Henrik Jörntell,et al.  Reciprocal Bidirectional Plasticity of Parallel Fiber Receptive Fields in Cerebellar Purkinje Cells and Their Afferent Interneurons , 2002, Neuron.

[52]  Hongkui Zeng,et al.  Forebrain-Specific Calcineurin Knockout Selectively Impairs Bidirectional Synaptic Plasticity and Working/Episodic-like Memory , 2001, Cell.

[53]  E. D’Angelo,et al.  Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum , 2001, Nature Neuroscience.

[54]  M. Meyer,et al.  Cre recombinase expression in cerebellar Purkinje cells , 2000, Genesis.

[55]  E. D'Angelo,et al.  Long-Term Potentiation of Intrinsic Excitability at the Mossy Fiber–Granule Cell Synapse of Rat Cerebellum , 2000, The Journal of Neuroscience.

[56]  D. Jaeger,et al.  The Control of Rate and Timing of Spikes in the Deep Cerebellar Nuclei by Inhibition , 2000, The Journal of Neuroscience.

[57]  D. Linden,et al.  Rapid, synaptically driven increases in the intrinsic excitability of cerebellar deep nuclear neurons , 2000, Nature Neuroscience.

[58]  V. Seutin,et al.  Recent advances in the pharmacology of quaternary salts of bicuculline. , 1999, Trends in pharmacological sciences.

[59]  S. Lisberger,et al.  Neural Learning Rules for the Vestibulo-Ocular Reflex , 1998, The Journal of Neuroscience.

[60]  D. Alkon,et al.  Intracellular Correlates of Acquisition and Long-Term Memory of Classical Conditioning in Purkinje Cell Dendrites in Slices of Rabbit Cerebellar Lobule HVI , 1998, The Journal of Neuroscience.

[61]  D. C. Hurst,et al.  Single-unit activity of cerebellar nuclear cells in the awake genetically dystonic rat , 1998, Neuroscience.

[62]  M. Häusser,et al.  Tonic Synaptic Inhibition Modulates Neuronal Output Pattern and Spatiotemporal Synaptic Integration , 1997, Neuron.

[63]  Lucien T. Thompson,et al.  Trace Eyeblink Conditioning Increases CA1 Excitability in a Transient and Learning-Specific Manner , 1996, The Journal of Neuroscience.

[64]  Douglas R. Wylie,et al.  More on climbing fiber signals and their consequence(s) , 1996 .

[65]  H. Jahnsen,et al.  Electrophysiological characteristics of neurones in the guinea‐pig deep cerebellar nuclei in vitro. , 1986, The Journal of physiology.

[66]  P. Dean,et al.  The cerebellar microcircuit as an adaptive filter: experimental and computational evidence , 2010, Nature Reviews Neuroscience.

[67]  R. Stackman,et al.  Small-Conductance Ca 2-Activated K Channel Type 2 ( SK 2 ) Modulates Hippocampal Learning , Memory , and Synaptic Plasticity , 2006 .

[68]  伊藤 正男 The cerebellum and neural control , 1984 .