Modulation of SK Channel Trafficking by Beta Adrenoceptors Enhances Excitatory Synaptic Transmission and Plasticity in the Amygdala

Emotionally arousing events are particularly well remembered. This effect is known to result from the release of stress hormones and activation of β adrenoceptors in the amygdala. However, the underlying cellular mechanisms are not understood. Small conductance calcium-activated potassium (SK) channels are present at glutamatergic synapses where they limit synaptic transmission and plasticity. Here, we show that β adrenoceptor activation regulates synaptic SK channels in lateral amygdala pyramidal neurons, through activation of protein kinase A. We show that SK channels are constitutively recycled from the postsynaptic membrane and that activation of β adrenoceptors removes SK channels from excitatory synapses. This results in enhanced synaptic transmission and plasticity. Our findings demonstrate a novel mechanism by which β adrenoceptors control synaptic transmission and plasticity, through regulation of SK channel trafficking, and suggest that modulation of synaptic SK channels may contribute to β adrenoceptor-mediated potentiation of emotional memories.

[1]  J M Bekkers,et al.  Apical Dendritic Location of Slow Afterhyperpolarization Current in Hippocampal Pyramidal Neurons: Implications for the Integration of Long-Term Potentiation , 1996, The Journal of Neuroscience.

[2]  Benno Roozendaal,et al.  Adrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences. , 2008, Progress in brain research.

[3]  P. Sah,et al.  Excitatory synaptic inputs to pyramidal neurons of the lateral amygdala , 1999, European Journal of Neuroscience.

[4]  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.

[5]  D. Paré,et al.  Glucocorticoids Enhance the Excitability of Principal Basolateral Amygdala Neurons , 2007, The Journal of Neuroscience.

[6]  S. Sever,et al.  Dynamin and endocytosis. , 2002, Current opinion in cell biology.

[7]  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.

[8]  James L. McGaugh,et al.  Norepinephrine Infused into the Basolateral Amygdala Posttraining Enhances Retention in a Spatial Water Maze Task , 1999, Neurobiology of Learning and Memory.

[9]  J. D. McGaugh The amygdala modulates the consolidation of memories of emotionally arousing experiences. , 2004, Annual review of neuroscience.

[10]  J. Storm,et al.  Regional Differences in Distribution and Functional Expression of Small-Conductance Ca2+-Activated K+ Channels in Rat Brain , 2002, The Journal of Neuroscience.

[11]  J. D. McGaugh,et al.  Role of norepinephrine in mediating stress hormone regulation of long-term memory storage: a critical involvement of the amygdala , 1999, Biological Psychiatry.

[12]  I. Spector,et al.  Latrunculins--novel marine macrolides that disrupt microfilament organization and affect cell growth: I. Comparison with cytochalasin D. , 1989, Cell motility and the cytoskeleton.

[13]  John E. Lisman,et al.  A Role of Actin Filament in Synaptic Transmission and Long-Term Potentiation , 1999, The Journal of Neuroscience.

[14]  Y. Humeau,et al.  Presynaptic induction of heterosynaptic associative plasticity in the mammalian brain , 2003, Nature.

[15]  J. Bizot,et al.  Apamin improves learning in an object recognition task in rats , 1997, Neuroscience Letters.

[16]  Rafael Yuste,et al.  Protein kinase A regulates calcium permeability of NMDA receptors , 2006, Nature Neuroscience.

[17]  J L McGaugh,et al.  Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Medvedev,et al.  Criteria for the evaluation of the functional importance of endogenous analogues of pharmacological regulators , 2007, Biomeditsinskaia khimiia.

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

[20]  Joseph E LeDoux,et al.  Distinct populations of NMDA receptors at subcortical and cortical inputs to principal cells of the lateral amygdala. , 1999, Journal of neurophysiology.

[21]  J. D. McGaugh,et al.  Beta-adrenergic activation and memory for emotional events. , 1994, Nature.

[22]  P W Gean,et al.  Isoproterenol potentiates synaptic transmission primarily by enhancing presynaptic calcium influx via P- and/or Q-type calcium channels in the rat amygdala , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  T. Moody,et al.  Activity-dependent beta-adrenergic modulation of low frequency stimulation induced LTP in the hippocampal CA1 region. , 1996, Neuron.

[24]  Yu Tian Wang,et al.  Regulation of AMPA Receptor–Mediated Synaptic Transmission by Clathrin-Dependent Receptor Internalization , 2000, Neuron.

[25]  R. Abagyan,et al.  Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity. , 2004, Bioorganic & medicinal chemistry letters.

[26]  Pankaj Sah,et al.  Physiological Role of Calcium-Activated Potassium Currents in the Rat Lateral Amygdala , 2002, The Journal of Neuroscience.

[27]  P. De Camilli,et al.  Dynamin and its partners: a progress report. , 1998, Current opinion in cell biology.

[28]  J. Cooper,et al.  Effects of cytochalasin and phalloidin on actin , 1987, The Journal of cell biology.

[29]  C. Jahr,et al.  Beta-adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase. , 1996, Neuron.

[30]  M. Min,et al.  Enhancement of Associative Long-Term Potentiation by Activation of β-Adrenergic Receptors at CA1 Synapses in Rat Hippocampal Slices , 2003, The Journal of Neuroscience.

[31]  Denis Paré,et al.  Lasting increases in basolateral amygdala activity after emotional arousal: implications for facilitated consolidation of emotional memories. , 2005, Learning & memory.

[32]  C. Hoogenraad,et al.  The postsynaptic architecture of excitatory synapses: a more quantitative view. , 2007, Annual review of biochemistry.

[33]  Eric R Kandel,et al.  Postsynaptic Induction and PKA-Dependent Expression of LTP in the Lateral Amygdala , 1998, Neuron.

[34]  John D E Gabrieli,et al.  Emotion enhances remembrance of neutral events past , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Joseph E LeDoux The Emotional Brain, Fear, and the Amygdala , 2003, Cellular and Molecular Neurobiology.

[36]  James L. McGaugh,et al.  Mechanisms of emotional arousal and lasting declarative memory , 1998, Trends in Neurosciences.

[37]  R. Malenka,et al.  AMPA receptor trafficking and synaptic plasticity. , 2002, Annual review of neuroscience.

[38]  P. Sah,et al.  Channels underlying neuronal calcium-activated potassium currents , 2002, Progress in Neurobiology.

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

[40]  Joseph E LeDoux,et al.  NMDA Receptors and L-Type Voltage-Gated Calcium Channels Contribute to Long-Term Potentiation and Different Components of Fear Memory Formation in the Lateral Amygdala , 2002, The Journal of Neuroscience.

[41]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[42]  Roberto Malinow,et al.  Emotion Enhances Learning via Norepinephrine Regulation of AMPA-Receptor Trafficking , 2007, Cell.

[43]  Edi Barkai,et al.  Learning‐induced modulation of SK channels‐mediated effect on synaptic transmission , 2007, The European journal of neuroscience.

[44]  R. Nicoll,et al.  Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. , 1990, Physiological reviews.

[45]  R. Nicoll,et al.  Contribution of cytoskeleton to the internalization of AMPA receptors. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Michael Davis,et al.  The amygdala: vigilance and emotion , 2001, Molecular Psychiatry.

[47]  D. Paré,et al.  Similar inhibitory processes dominate the responses of cat lateral amygdaloid projection neurons to their various afferents. , 1997, Journal of neurophysiology.

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

[49]  J A Conchello,et al.  Superresolution and convergence properties of the expectation-maximization algorithm for maximum-likelihood deconvolution of incoherent images. , 1998, Journal of the Optical Society of America. A, Optics, image science, and vision.

[50]  Y. Goda,et al.  The actin cytoskeleton: integrating form and function at the synapse. , 2005, Annual review of neuroscience.

[51]  J. D. McGaugh,et al.  Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance in rats , 2002, The European journal of neuroscience.

[52]  P. Sah,et al.  Distribution of IP3‐mediated calcium responses and their role in nuclear signalling in rat basolateral amygdala neurons , 2007, The Journal of physiology.

[53]  Yan Li,et al.  Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses , 2007, Proceedings of the National Academy of Sciences.

[54]  Mark J. Thomas,et al.  Activity-Dependent β-Adrenergic Modulation of Low Frequency Stimulation Induced LTP in the Hippocampal CA1 Region , 1996, Neuron.

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

[56]  P. Pedarzani,et al.  Differential Distribution of Three Ca2+-Activated K+ Channel Subunits, SK1, SK2, and SK3, in the Adult Rat Central Nervous System , 2000, Molecular and Cellular Neuroscience.

[57]  R. Abagyan,et al.  Small molecule inhibitors of dynamin I GTPase activity: development of dimeric tyrphostins. , 2005, Journal of medicinal chemistry.

[58]  M. Kneussel Dynamic regulation of GABAA receptors at synaptic sites , 2002, Brain Research Reviews.

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

[60]  J. D. McGaugh,et al.  Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[61]  W. Regehr,et al.  Short-term synaptic plasticity. , 2002, Annual review of physiology.

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

[63]  C. Jahr,et al.  β-Adrenergic Regulation of Synaptic NMDA Receptors by cAMP-Dependent Protein Kinase , 1996, Neuron.

[64]  S. Moss,et al.  Modulation of GABAA receptor activity by phosphorylation and receptor trafficking: implications for the efficacy of synaptic inhibition , 2003, Current Opinion in Neurobiology.

[65]  Joseph E LeDoux,et al.  New vistas on amygdala networks in conditioned fear. , 2004, Journal of neurophysiology.

[66]  J. D. McGaugh,et al.  Modulating effects of posttraining epinephrine on memory: Involvement of the amygdala noradrenergic system , 1986, Brain Research.

[67]  J. Power,et al.  The amygdaloid complex: anatomy and physiology. , 2003, Physiological reviews.

[68]  A. Gilman,et al.  G proteins: transducers of receptor-generated signals. , 1987, Annual review of biochemistry.