Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses

Emotional arousal, linked to a surge of norepinephrine (NE) in the amygdala, leads to creation of stronger and longer-lasting memories. However, little is known about the synaptic mechanisms of such modulatory NE influences. Long-term potentiation (LTP) in auditory inputs to the lateral nucleus of the amygdala was recently linked to the acquisition of fear memory. Therefore we explored whether LTP induction at thalamo-amygdala projections, conveying the acoustic conditioned stimulus information to the amygdala during fear conditioning, is under adrenergic control. Using whole-cell recordings from amygdala slices, we show that NE suppresses GABAergic inhibition of projection neurons in the lateral amygdala and enables the induction of LTP at thalamo-amygdala synapses under conditions of intact GABAA receptor-mediated inhibition. Our data indicate that the NE effects on the efficacy of inhibition could result from a decrease in excitability of local circuit interneurons, without direct effects of NE on release machinery of the GABA-containing vesicles or the size of single-quanta postsynaptic GABAA receptor-mediated responses. Thus, adrenergic modulation of local interneurons may contribute to the formation of fear memory by gating LTP in the conditioned stimulus pathways.

[1]  Eric R. Kandel,et al.  Identification of a Signaling Network in Lateral Nucleus of Amygdala Important for Inhibiting Memory Specifically Related to Learned Fear , 2002, Cell.

[2]  E. Pralong,et al.  Noradrenaline Modulates GIutamate‐mediated Neurotransmission in the Rat Basolateral Amygdala In Vitro , 1997, The European journal of neuroscience.

[3]  Joseph E LeDoux,et al.  Postsynaptic Receptor Trafficking Underlying a Form of Associative Learning , 2005, Science.

[4]  James L. McGaugh,et al.  Enhancement of extinction memory consolidation: The role of the noradrenergic and GABAergic systems within the basolateral amygdala , 2006, Neurobiology of Learning and Memory.

[5]  E. Tsvetkov,et al.  Spatiotemporal Asymmetry of Associative Synaptic Plasticity in Fear Conditioning Pathways , 2006, Neuron.

[6]  C. Parsons,et al.  a2-Adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o-protein-mediated modulation of Ca2þ-channels and inwardly rectifying Kþ-channels in LTD , 2003 .

[7]  C. Harley,et al.  Locus Ceruleus Activation Suppresses Feedforward Interneurons and Reduces β-γ Electroencephalogram Frequencies While It Enhances θ Frequencies in Rat Dentate Gyrus , 2005, The Journal of Neuroscience.

[8]  O. Lindvall,et al.  The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. , 1974, Acta physiologica Scandinavica. Supplementum.

[9]  J. D. McGaugh Memory--a century of consolidation. , 2000, Science.

[10]  Y. Humeau,et al.  Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition , 2003, Nature Neuroscience.

[11]  Eric R. Kandel,et al.  Fear Conditioning Occludes LTP-Induced Presynaptic Enhancement of Synaptic Transmission in the Cortical Pathway to the Lateral Amygdala , 2002, Neuron.

[12]  M. McKERNAN,et al.  Fear conditioning induces a lasting potentiation of synaptic currents in vitro , 1997, Nature.

[13]  E R Kandel,et al.  Both Protein Kinase A and Mitogen-Activated Protein Kinase Are Required in the Amygdala for the Macromolecular Synthesis-Dependent Late Phase of Long-Term Potentiation , 2000, The Journal of Neuroscience.

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

[15]  E. Kandel,et al.  stathmin, a Gene Enriched in the Amygdala, Controls Both Learned and Innate Fear , 2005, Cell.

[16]  Sean T. Manion,et al.  Stress Impairs α1A Adrenoceptor-Mediated Noradrenergic Facilitation of GABAergic Transmission in the Basolateral Amygdala , 2004, Neuropsychopharmacology.

[17]  James L. McGaugh,et al.  β-Adrenergic activation and memory for emotional events , 1994, Nature.

[18]  E. Tsvetkov,et al.  Glutamate Uptake Determines Pathway Specificity of Long-Term Potentiation in the Neural Circuitry of Fear Conditioning , 2004, Neuron.

[19]  Joseph E LeDoux Emotion Circuits in the Brain , 2000 .

[20]  Joseph E LeDoux,et al.  Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala , 2004, Neuroscience.

[21]  P. Shinnick‐Gallagher,et al.  Fear learning induces persistent facilitation of amygdala synaptic transmission , 2005, The European journal of neuroscience.

[22]  H. Schnitzler,et al.  Clonidine injections into the lateral nucleus of the amygdala block acquisition and expression of fear‐potentiated startle , 2002, The European journal of neuroscience.

[23]  F. Chen,et al.  Locus coeruleus activation by foot shock or electrical stimulation inhibits amygdala neurons , 2007, Neuroscience.

[24]  S. Thomas,et al.  A Distinct Role for Norepinephrine in Memory Retrieval , 2004, Cell.

[25]  P. Sah,et al.  Independent roles of calcium and voltage‐dependent potassium currents in controlling spike frequency adaptation in lateral amygdala pyramidal neurons , 2005, The European journal of neuroscience.

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

[27]  G. Quirk,et al.  Neuronal signalling of fear memory , 2004, Nature Reviews Neuroscience.

[28]  Joseph E LeDoux,et al.  Fear conditioning induces associative long-term potentiation in the amygdala , 1997, Nature.