SK2 channel plasticity contributes to LTP at Schaffer collateral–CA1 synapses

Long-term potentiation (LTP) of synaptic strength at Schaffer collateral synapses has largely been attributed to changes in the number and biophysical properties of AMPA receptors (AMPARs). Small-conductance Ca2+-activated K+ channels (SK2 channels) are functionally coupled with NMDA receptors (NMDARs) in CA1 spines such that their activity modulates the shape of excitatory postsynaptic potentials (EPSPs) and increases the threshold for induction of LTP. Here we show that LTP induction in mouse hippocampus abolishes SK2 channel activity in the potentiated synapses. This effect is due to SK2 channel internalization from the postsynaptic density (PSD) into the spine. Blocking PKA or cell dialysis with a peptide representing the C-terminal domain of SK2 that contains three known PKA phosphorylation sites blocks the internalization of SK2 channels after LTP induction. Thus the increase in AMPARs and the decrease in SK2 channels combine to produce the increased EPSP underlying LTP.

[1]  E. Bienenstock,et al.  Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  G. Collingridge,et al.  The antagonism of amino acid‐induced excitations of rat hippocampal CA1 neurones in vitro. , 1983, The Journal of physiology.

[3]  J. Lisman,et al.  A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Nicoll,et al.  An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation , 1989, Nature.

[5]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[6]  R. Nicoll,et al.  NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms , 1993, Trends in Neurosciences.

[7]  M. Bear,et al.  Mechanism for a sliding synaptic modification threshold , 1995, Neuron.

[8]  N. Marrion,et al.  Small-Conductance, Calcium-Activated Potassium Channels from Mammalian Brain , 1996, Science.

[9]  Eric R. Kandel,et al.  Recruitment of New Sites of Synaptic Transmission During the cAMP-Dependent Late Phase of LTP at CA3–CA1 Synapses in the Hippocampus , 1997, Neuron.

[10]  Andreas Lüthi,et al.  Modulation of AMPA receptor unitary conductance by synaptic activity , 1998, Nature.

[11]  Masahiko Watanabe,et al.  Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fibre‐recipient layer) of the mouse hippocampal CA3 subfield , 1998, The European journal of neuroscience.

[12]  D. Faber,et al.  Ca2+/calmodulin-dependent kinase II mediates simultaneous enhancement of gap-junctional conductance and glutamatergic transmission. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Shenolikar,et al.  Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. , 1998, Science.

[14]  T. Soderling,et al.  Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Nicoll,et al.  Long-term potentiation--a decade of progress? , 1999, Science.

[16]  S. Shenolikar,et al.  Long-Term Potentiation Induced by θ Frequency Stimulation Is Regulated by a Protein Phosphatase-1-Operated Gate , 2000, The Journal of Neuroscience.

[17]  M. Ehlers,et al.  Reinsertion or Degradation of AMPA Receptors Determined by Activity-Dependent Endocytic Sorting , 2000, Neuron.

[18]  V. Piëch,et al.  Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons , 2001, Nature Neuroscience.

[19]  I. Song,et al.  Regulation of AMPA receptors during synaptic plasticity , 2002, Trends in Neurosciences.

[20]  J. Lisman,et al.  The molecular basis of CaMKII function in synaptic and behavioural memory , 2002, Nature Reviews Neuroscience.

[21]  Eric R. Kandel,et al.  Expression of Constitutively Active CREB Protein Facilitates the Late Phase of Long-Term Potentiation by Enhancing Synaptic Capture , 2002, Cell.

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

[23]  B. Sakmann,et al.  Molecular dissection of hippocampal theta-burst pairing potentiation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Karel Svoboda,et al.  Plasticity of calcium channels in dendritic spines , 2003, Nature Neuroscience.

[25]  Gavin Rumbaugh,et al.  Phosphorylation of the AMPA Receptor GluR1 Subunit Is Required for Synaptic Plasticity and Retention of Spatial Memory , 2003, Cell.

[26]  Roberto Malinow,et al.  PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity , 2003, Nature Neuroscience.

[27]  R. Nicoll,et al.  AMPA Receptor Trafficking at Excitatory Synapses , 2003, Neuron.

[28]  G. Buzsáki,et al.  Place Representation within Hippocampal Networks Is Modified by Long-Term Potentiation , 2003, Neuron.

[29]  Mikyoung Park,et al.  Recycling Endosomes Supply AMPA Receptors for LTP , 2004, Science.

[30]  J. Lisman,et al.  Contribution of Ih and GABAB to synaptically induced afterhyperpolarizations in CA1: a brake on the NMDA response. , 2004, Journal of neurophysiology.

[31]  G. Collingridge,et al.  Receptor trafficking and synaptic plasticity , 2004, Nature Reviews Neuroscience.

[32]  Scott M Thompson,et al.  Unique roles of SK and Kv4.2 potassium channels in dendritic integration. , 2004, Neuron.

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

[34]  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.

[35]  Maiken Nedergaard,et al.  Activity-Dependent Long-Term Potentiation of Intrinsic Excitability in Hippocampal CA1 Pyramidal Neurons , 2005, The Journal of Neuroscience.

[36]  P. Sah,et al.  SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala , 2005, Nature Neuroscience.

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

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

[39]  M. Ehlers,et al.  Organelles and trafficking machinery for postsynaptic plasticity. , 2006, Annual review of neuroscience.

[40]  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.

[41]  Agnès Gruart,et al.  Involvement of the CA3–CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice , 2006, The Journal of Neuroscience.

[42]  Jonathan R. Whitlock,et al.  Learning Induces Long-Term Potentiation in the Hippocampus , 2006, Science.

[43]  Tobias Bonhoeffer,et al.  Homeostatic shutdown of long-term potentiation in the adult hippocampus. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[44]  T. Soderling,et al.  Extrasynaptic Membrane Trafficking Regulated by GluR1 Serine 845 Phosphorylation Primes AMPA Receptors for Long-term Potentiation* , 2006, Journal of Biological Chemistry.

[45]  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.

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

[47]  B. Sabatini,et al.  Nonlinear Regulation of Unitary Synaptic Signals by CaV2.3 Voltage-Sensitive Calcium Channels Located in Dendritic Spines , 2007, Neuron.

[48]  T. Soderling,et al.  Regulatory mechanisms of AMPA receptors in synaptic plasticity , 2007, Nature Reviews Neuroscience.

[49]  Sung-Cherl Jung,et al.  Regulation of Dendritic Excitability by Activity-Dependent Trafficking of the A-Type K+ Channel Subunit Kv4.2 in Hippocampal Neurons , 2007, Neuron.

[50]  R. K. Simpson.  Nature Neuroscience , 2022 .