Neurochemistry/Neuropharmacology of Fear and Fear Conditioning

Over the last 20 years, research on emotion has enjoyed a resurgence in the neurosciences. Nowhere has this been more evident than in the fear system of the brain. In this chapter, we discuss the brain's “fear learning” system from a neurochemical and pha

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REPORT


Neurochemistry/ Neuropharmacology of Fear and Fear Conditioning

G. E. Schafe . J. E. LeDoux

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690 1.1 The Amygdala and Fear Conditioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 691 2 Neurochemical Mechanisms of Fear Memory Formation: The Importance of LTP . . . . . . . . . . . . 692 2.1 Early‐LTP Versus Late‐LTP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 692 3 3.1 3.2 3.3 3.4

Neurochemical Mechanisms Underlying Acquisition and STM Formation of Fear Conditioning in the Amygdala . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 693 NMDA Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 693 Metabotropic Glutamate Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 694 Ca2þ/Calmodulin‐Dependent Protein Kinase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 696 AMPA Receptor Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 696

4 4.1 4.2 4.3

Neurochemical Mechanisms of LTM Formation in the Amygdala . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 696 L‐type VGCCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 697 Protein Kinase A and Mitogen‐Activated Protein Kinase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 697 Transcriptional Regulation and Macromolecular Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698

5

A Model of Fear Memory Acquisition and Consolidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 701

6

Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 702

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Springer-Verlag Berlin Heidelberg 2007

690

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Neurochemistry/neuropharmacology of fear and fear conditioning

Abstract: Over the last 20 years, research on emotion has enjoyed a resurgence in the neurosciences. Nowhere has this been more evident than in the fear system of the brain. In this chapter, we discuss the brain’s ‘‘fear learning’’ system from a neurochemical and pharmacological perspective. We focus on the neurochemical and biochemical