Neuronal signalling of fear memory

The learning and remembering of fearful events depends on the integrity of the amygdala, but how are fear memories represented in the activity of amygdala neurons? Here, we review recent electrophysiological studies indicating that neurons in the lateral amygdala encode aversive memories during the acquisition and extinction of Pavlovian fear conditioning. Studies that combine unit recording with brain lesions and pharmacological inactivation provide evidence that the lateral amygdala is a crucial locus of fear memory. Extinction of fear memory reduces associative plasticity in the lateral amygdala and involves the hippocampus and prefrontal cortex. Understanding the signalling of aversive memory by amygdala neurons opens new avenues for research into the neural systems that support fear behaviour.

[1]  R. Galamboš,et al.  Extralemniscal activation of auditory cortex in cats. , 1961, The American journal of physiology.

[2]  W. D. Neff,et al.  EXPERIMENTAL PROCEDURES AFFECTING EVOKED RESPONSES RECORDED FROM AUDITORY CORTEX. , 1963, Electroencephalography and clinical neurophysiology.

[3]  W. R. Adey,et al.  RESPONSE PATTERNS OF THALAMIC NEURONS DURING CLASSICAL CONDITIONING. , 1964, Electroencephalography and clinical neurophysiology.

[4]  R. Mark,et al.  Fear and the modification of acoustically evoked potentials during conditioning. , 1967, Journal of neurophysiology.

[5]  S. S. Fox,et al.  Single-cell activity in cat motor cortex. I. Modifications during classical conditioning procedures. , 1969, Journal of neurophysiology.

[6]  C. Woody,et al.  Conditioned eye blink: unit activity at coronal-precruciate cortex of the cat. , 1970, Journal of neurophysiology.

[7]  T. Imig,et al.  Modification of unit discharges in the medial geniculate nucleus by click-shock pairing. , 1972, Experimental neurology.

[8]  James L Olds,et al.  Differential development of conditioned unit changes in thalamus and cortex of rat. , 1972, Journal of neurophysiology.

[9]  J F Disterhoft,et al.  Learning centers of rat brain mapped by measuring latencies of conditioned unit responses. , 1972, Journal of neurophysiology.

[10]  Y. Ben-Ari,et al.  Plasticity at unitary level. II. Modifications during sensory-sensory association procedures. , 1972, Electroencephalography and clinical neurophysiology.

[11]  Y. Ben-Ari,et al.  Lateral amygdala unit activity: II. Habituating and non-habituating neurons. , 1974, Electroencephalography and clinical neurophysiology.

[12]  N. Weinberger,et al.  Modification of auditory and somatosensory system activity during pupillary conditioning in the paralyzed cat. , 1975, Journal of neurophysiology.

[13]  M. Gabriel,et al.  Short-latency discriminative unit response: Engram or bias? , 1976 .

[14]  J. Disterhoft,et al.  Trial sequence of changed unit activity in auditory system of alert rat during conditioned response acquisition and extinction. , 1976, Journal of neurophysiology.

[15]  J. Price,et al.  A description of the amygdaloid complex in the rat and cat with observations on intra‐amygdaloid axonal connections , 1978, The Journal of comparative neurology.

[16]  Michela Gallagher,et al.  Amygdala central nucleus lesions: Effect on heart rate conditioning in the rabbit , 1979, Physiology & Behavior.

[17]  Timothy A. Salthouse,et al.  Acquisition and Retention , 1982 .

[18]  M. Gallagher,et al.  Multiple unit activity recorded from amygdala central nucleus during Pavlovian heart rate conditioning in rabbit , 1982, Brain Research.

[19]  J L McGaugh,et al.  Hormonal influences on memory. , 1983, Annual review of psychology.

[20]  A Sakaguchi,et al.  Subcortical efferent projections of the medial geniculate nucleus mediate emotional responses conditioned to acoustic stimuli , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  Joseph E LeDoux,et al.  Projections to the subcortical forebrain from anatomically defined regions of the medial geniculate body in the rat , 1985, The Journal of comparative neurology.

[22]  Jeffrey P. Pascoe,et al.  Electrophysiological characteristics of amygdaloid central nucleus neurons during Pavlovian fear conditioning in the rabbit , 1985, Behavioural Brain Research.

[23]  Joseph E LeDoux,et al.  Interruption of projections from the medial geniculate body to an archi-neostriatal field disrupts the classical conditioning of emotional responses to acoustic stimuli , 1986, Neuroscience.

[24]  Joseph E LeDoux,et al.  Intrinsic neurons in the amygdaloid field projected to by the medial geniculate body mediate emotional responses conditioned to acoustic stimuli , 1986, Brain Research.

[25]  Joseph E LeDoux,et al.  The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  Joseph E LeDoux,et al.  Synaptic plasticity in fear conditioning circuits: induction of LTP in the lateral nucleus of the amygdala by stimulation of the medial geniculate body , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  Michael Davis,et al.  Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala , 1990, Nature.

[28]  J. Edeline,et al.  Discriminative long-term retention of rapidly induced multiunit changes in the hippocampus, medial geniculate and auditory cortex , 1990, Behavioural Brain Research.

[29]  E. W. Kairiss,et al.  Long‐Term synaptic potentiation in the amygdala , 1990, Synapse.

[30]  Joseph E LeDoux,et al.  Topographic organization of neurons in the acoustic thalamus that project to the amygdala , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  Joseph E. LeDoux,et al.  Overlapping projections to the amygdala and striatum from auditory processing areas of the thalamus and cortex , 1991, Neuroscience Letters.

[32]  Michael Davis,et al.  Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  이기수,et al.  II. , 1992 .

[34]  J. Edeline,et al.  Associative retuning in the thalamic source of input to the amygdala and auditory cortex: receptive field plasticity in the medial division of the medial geniculate body. , 1992, Behavioral neuroscience.

[35]  E. Capaldi,et al.  The organization of behavior. , 1992, Journal of applied behavior analysis.

[36]  Joseph E LeDoux,et al.  Equipotentiality of thalamo-amygdala and thalamo-cortico-amygdala circuits in auditory fear conditioning , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  Joseph E LeDoux,et al.  Information cascade from primary auditory cortex to the amygdala: corticocortical and corticoamygdaloid projections of temporal cortex in the rat. , 1993, Cerebral cortex.

[38]  M. Bouton,et al.  Effects of Contextual Conditioning and Unconditional Stimulus Presentation on Performance in Appetitive Conditioning , 1993, The Quarterly journal of experimental psychology. B, Comparative and physiological psychology.

[39]  Joseph E. LeDoux,et al.  Extinction of emotional learning: Contribution of medial prefrontal cortex , 1993, Neuroscience Letters.

[40]  Richard G. Bingham,et al.  The next steps , 1993, Other Conferences.

[41]  Joseph E LeDoux,et al.  Somatosensory and auditory convergence in the lateral nucleus of the amygdala. , 1993, Behavioral neuroscience.

[42]  P. Bellgowan,et al.  Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. , 1994, Behavioral neuroscience.

[43]  T. Ono,et al.  Neuronal responsiveness to various sensory stimuli, and associative learning in the rat amygdala , 1995, Neuroscience.

[44]  Joseph E LeDoux,et al.  Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: Parallel recordings in the freely behaving rat , 1995, Neuron.

[45]  M. Fanselow,et al.  Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  Joseph E LeDoux,et al.  Convergent but temporally separated inputs to lateral amygdala neurons from the auditory thalamus and auditory cortex use different postsynaptic receptors: in vivo intracellular and extracellular recordings in fear conditioning pathways. , 1996, Learning & memory.

[47]  M. Fanselow,et al.  N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats. , 1996, Behavioral neuroscience.

[48]  Joseph E LeDoux,et al.  Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala , 1997, Trends in Neurosciences.

[49]  Joseph E LeDoux,et al.  NMDA and AMPA receptors in the lateral nucleus of the amygdala are postsynaptic to auditory thalamic afferents , 1997, Synapse.

[50]  Joseph E LeDoux,et al.  How the Brain Processes Emotional Information , 1997, Annals of the New York Academy of Sciences.

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

[52]  Joseph E LeDoux,et al.  Fear Conditioning Enhances Different Temporal Components of Tone-Evoked Spike Trains in Auditory Cortex and Lateral Amygdala , 1997, Neuron.

[53]  Joseph E LeDoux,et al.  Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli. , 1997, Behavioral neuroscience.

[54]  T. Robbins,et al.  Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala , 1997, Nature.

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

[56]  Joseph E LeDoux,et al.  Differential Effects of Amygdala Lesions on Early and Late Plastic Components of Auditory Cortex Spike Trains during Fear Conditioning , 1998, The Journal of Neuroscience.

[57]  J. D. McGaugh,et al.  Basolateral amygdala is not critical for cognitive memory of contextual fear conditioning. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[58]  D. Paré,et al.  Intrinsic circuitry of the amygdaloid complex: common principles of organization in rats and cats , 1998, Trends in Neurosciences.

[59]  Joseph E LeDoux,et al.  Functional Inactivation of the Amygdala before But Not after Auditory Fear Conditioning Prevents Memory Formation , 1999, The Journal of Neuroscience.

[60]  Joseph E LeDoux,et al.  Why We Think Plasticity Underlying Pavlovian Fear Conditioning Occurs in the Basolateral Amygdala , 1999, Neuron.

[61]  Marzia Martina,et al.  An Inhibitory Interface Gates Impulse Traffic between the Input and Output Stations of the Amygdala , 1999, The Journal of Neuroscience.

[62]  Stephen Maren,et al.  Long-term potentiation in the amygdala: a mechanism for emotional learning and memory , 1999, Trends in Neurosciences.

[63]  G. Quirk,et al.  The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear , 2000, The Journal of Neuroscience.

[64]  D. Paré,et al.  Neuronal Correlates of Fear in the Lateral Amygdala: Multiple Extracellular Recordings in Conscious Cats , 2000, The Journal of Neuroscience.

[65]  L. Cahill,et al.  Neurobiological mechanisms of emotionally influenced, long-term memory. , 2000, Progress in brain research.

[66]  H. Pape,et al.  Putative Cortical and Thalamic Inputs Elicit Convergent Excitation in a Population of GABAergic Interneurons of the Lateral Amygdala , 2000, The Journal of Neuroscience.

[67]  Joseph E LeDoux.  Emotion circuits in the brain. , 2009, Annual review of neuroscience.

[68]  Stephen Maren,et al.  Auditory fear conditioning increases CS‐elicited spike firing in lateral amygdala neurons even after extensive overtraining , 2000, The European journal of neuroscience.

[69]  J. Glowinski,et al.  Hippocampo‐prefrontal cortex pathway: Anatomical and electrophysiological characteristics , 2000, Hippocampus.

[70]  D. Paré,et al.  Differential fear conditioning induces reciprocal changes in the sensory responses of lateral amygdala neurons to the CS(+) and CS(-). , 2000, Learning & memory.

[71]  A. Ylinen,et al.  Reciprocal Connections between the Amygdala and the Hippocampal Formation, Perirhinal Cortex, and Postrhinal Cortex in Rat: A Review , 2000, Annals of the New York Academy of Sciences.

[72]  Amy Poremba,et al.  Amygdalar Efferents Initiate Auditory Thalamic Discriminative Training-Induced Neuronal Activity , 2001, The Journal of Neuroscience.

[73]  M. Fendt,et al.  Injections of the NMDA Receptor Antagonist Aminophosphonopentanoic Acid into the Lateral Nucleus of the Amygdala Block the Expression of Fear-Potentiated Startle and Freezing , 2001, The Journal of Neuroscience.

[74]  Stephen Maren,et al.  Hippocampal Inactivation Disrupts Contextual Retrieval of Fear Memory after Extinction , 2001, The Journal of Neuroscience.

[75]  S. Mineka,et al.  A modern learning theory perspective on the etiology of panic disorder. , 2001, Psychological review.

[76]  Stephen Maren.  Neurobiology of Pavlovian fear conditioning. , 2001, Annual review of neuroscience.

[77]  H. T. Blair,et al.  Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. , 2001, Learning & memory.

[78]  Theresa M. Desrochers,et al.  Two different lateral amygdala cell populations contribute to the initiation and storage of memory , 2001, Nature Neuroscience.

[79]  Michael Davis,et al.  Mitogen-Activated Protein Kinase Cascade in the Basolateral Nucleus of Amygdala Is Involved in Extinction of Fear-Potentiated Startle , 2001, The Journal of Neuroscience.

[80]  Karim Nader,et al.  Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective , 2001, Trends in Neurosciences.

[81]  Joseph E LeDoux,et al.  Intra-Amygdala Blockade of the NR2B Subunit of the NMDA Receptor Disrupts the Acquisition But Not the Expression of Fear Conditioning , 2001, The Journal of Neuroscience.

[82]  Stephen Maren,et al.  The Amygdala Is Essential for the Development of Neuronal Plasticity in the Medial Geniculate Nucleus during Auditory Fear Conditioning in Rats , 2001, The Journal of Neuroscience.

[83]  A. Grace,et al.  Dopamine-mediated modulation of odour-evoked amygdala potentials during pavlovian conditioning , 2002, Nature.

[84]  B. Rothbaum,et al.  Exposure therapy for posttraumatic stress disorder. , 2002, American journal of psychotherapy.

[85]  G. Quirk,et al.  Neurons in medial prefrontal cortex signal memory for fear extinction , 2002, Nature.

[86]  Michael Davis,et al.  Behavioral and Neural Analysis of Extinction , 2002, Neuron.

[87]  G. Quirk.  Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery. , 2002, Learning & memory.

[88]  C. Herry,et al.  Prefrontal Cortex Long-Term Potentiation, But Not Long-Term Depression, Is Associated with the Maintenance of Extinction of Learned Fear in Mice , 2002, The Journal of Neuroscience.

[89]  Sidarta Ribeiro,et al.  Multielectrode recordings: the next steps , 2002, Current Opinion in Neurobiology.

[90]  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.

[91]  Joseph E LeDoux,et al.  Parallels between cerebellum- and amygdala-dependent conditioning , 2002, Nature Reviews Neuroscience.

[92]  Laura Bennett,et al.  The next steps. , 2003, BMJ.

[93]  Jennifer A. Hobin,et al.  Auditory-Evoked Spike Firing in the Lateral Amygdala and Pavlovian Fear Conditioning Mnemonic Code or Fear Bias? , 2003, Neuron.

[94]  Hans-Christian Pape,et al.  Amygdalar and Hippocampal Theta Rhythm Synchronization During Fear Memory Retrieval , 2003, Science.

[95]  D. Paré,et al.  Stimulation of Medial Prefrontal Cortex Decreases the Responsiveness of Central Amygdala Output Neurons , 2003, The Journal of Neuroscience.

[96]  Jennifer A. Hobin,et al.  Context-Dependent Neuronal Activity in the Lateral Amygdala Represents Fear Memories after Extinction , 2003, The Journal of Neuroscience.

[97]  Richard F. Thompson,et al.  Neural substrates of eyeblink conditioning: acquisition and retention. , 2003, Learning & memory.

[98]  A. Grace,et al.  The Prefrontal Cortex Regulates Lateral Amygdala Neuronal Plasticity and Responses to Previously Conditioned Stimuli , 2003, The Journal of Neuroscience.

[99]  N. Weinberger.  Specific long-term memory traces in primary auditory cortex , 2004, Nature Reviews Neuroscience.

[100]  G. Quirk,et al.  Delayed recall of fear extinction in rats with lesions of ventral medial prefrontal cortex. , 2004, Learning & memory.

[101]  G. Quirk.  Learning not to fear, faster. , 2004, Learning & memory.

[102]  G. Quirk,et al.  Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner. , 2004, Behavioral neuroscience.

[103]  Joseph E LeDoux,et al.  Response properties of single units in areas of rat auditory thalamus that project to the amygdala , 2004, Experimental Brain Research.

[104]  G. Buzsáki.  Large-scale recording of neuronal ensembles , 2004, Nature Neuroscience.

[105]  G. Holstege,et al.  Amygdaloid projections to the mesencephalon, pons and medulla oblongata in the cat , 1978, Experimental Brain Research.

[106]  D. Paré,et al.  Role of amygdala oscillations in the consolidation of emotional memories , 2004, Biological Psychiatry.

[107]  Stephen Maren,et al.  NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala , 2004, The European journal of neuroscience.

[108]  J. D. McGaugh,et al.  The Basolateral Amygdala Interacts with the Medial Prefrontal Cortex in Regulating Glucocorticoid Effects on Working Memory Impairment , 2004, The Journal of Neuroscience.

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