Auditory fear conditioning increases CS‐elicited spike firing in lateral amygdala neurons even after extensive overtraining

We examined the influence of extensive overtraining (75 trials) of auditory fear conditioning on the expression of conditional stimulus (CS)‐elicited spike firing in lateral amygdala (LA) neurons. Single units were recorded from chronic multichannel electrodes implanted in the LA of conscious and freely moving rats. In sequential training sessions, the rats received either five or 70 fear conditioning trials, which consisted of a white‐noise CS and a coterminating footshock unconditional stimulus (US). Unpaired (sensitization) controls received the same number of trials, but the CS and US were explicitly unpaired. Paired CS–US presentations yielded robust increases in CS‐elicited spike firing in LA neurons after both five and 70 conditioning trials, and the magnitude of the spike firing increases was correlated with the expression of conditional freezing to the CS. After 75 training trials, maximal conditioning‐related increases in LA firing were exhibited within 20 ms of CS onset, indicating that this increase is mediated by direct thalamo‐amygdala projections. There was no significant increase in CS‐elicited spike firing or freezing behaviour in the unpaired group. These results complement amygdala lesion studies [e.g. Maren, S. (1999a) J. Neurosci., 19, 8696–8703] and support the view that the basolateral complex of the amygdala is involved in the encoding and storage of fear memories even after extensive overtraining.

[1]  Joseph E LeDoux,et al.  Human Amygdala Activation during Conditioned Fear Acquisition and Extinction: a Mixed-Trial fMRI Study , 1998, Neuron.

[2]  E. J. Green,et al.  Simultaneous single unit recording in the medial nucleus of the medial geniculate nucleus and amygdaloid central nucleus throughout habituation, acquisition, and extinction of the rabbit's classically conditioned heart rate , 1995, Brain Research.

[3]  James L McGaugh,et al.  Post-training amygdaloid lesions impair retention of an inhibitory avoidance response , 1982, Behavioural Brain Research.

[4]  J. D. McGaugh,et al.  Is the Amygdala a Locus of “Conditioned Fear”? Some Questions and Caveats , 1999, Neuron.

[5]  S. Mineka,et al.  Dissociation between conditioned emotional response and extended avoidance performance , 1980 .

[6]  J. D. McGaugh,et al.  The Effects of Intra-amygdala Infusion of the AMPA Receptor Antagonist CNQX on Retention Performance Following Aversive Training , 1996, Neurobiology of Learning and Memory.

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

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

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

[10]  M. Fanselow,et al.  The Amygdala and Fear Conditioning: Has the Nut Been Cracked? , 1996, Neuron.

[11]  Joseph E LeDoux,et al.  Organization of projections to the lateral amygdala from auditory and visual areas of the thalamus in the rat , 1999, The Journal of comparative neurology.

[12]  M. Davis,et al.  Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  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.

[14]  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.

[15]  Y. Lee,et al.  Lack of a temporal gradient of retrograde amnesia following NMDA-induced lesions of the basolateral amygdala assessed with the fear-potentiated startle paradigm. , 1996, Behavioral neuroscience.

[16]  Joseph E LeDoux,et al.  Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus , 2000, Nature Neuroscience.

[17]  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.

[18]  J. D. McGaugh,et al.  Increased training in an aversively motivated task attenuates the memory-impairing effects of posttraining N-methyl-D-aspartate-induced amygdala lesions. , 1992, Behavioral neuroscience.

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

[20]  Bruce L. McNaughton,et al.  The stereotrode: A new technique for simultaneous isolation of several single units in the central nervous system from multiple unit records , 1983, Journal of Neuroscience Methods.

[21]  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 .

[22]  Karl J. Friston,et al.  Brain Systems Mediating Aversive Conditioning: an Event-Related fMRI Study , 1998, Neuron.

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

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

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

[26]  M. Gabriel,et al.  Amygdala Neurons Mediate Acquisition But Not Maintenance of Instrumental Avoidance Behavior in Rabbits , 1999, The Journal of Neuroscience.

[27]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[28]  M. Fanselow,et al.  Retrograde abolition of conditional fear after excitotoxic lesions in the basolateral amygdala of rats: absence of a temporal gradient. , 1996, Behavioral neuroscience.

[29]  J. D. McGaugh,et al.  Memory of rats with amygdala lesions induced 30 days after footshock-motivated escape training reflects degree of original training. , 1994, Behavioral neuroscience.

[30]  J. Edeline,et al.  Stimulation at a site of auditory-somatosensory convergence in the medial geniculate nucleus is an effective unconditioned stimulus for fear conditioning. , 1992, Behavioral neuroscience.

[31]  T. Robbins,et al.  Complementary roles for the amygdala and hippocampus in aversive conditioning to explicit and contextual cues , 1991, Neuroscience.

[32]  M. Gabriel,et al.  Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits , 1991, Brain Research.

[33]  Michael Davis,et al.  Neurobiology of fear responses: the role of the amygdala. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

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

[35]  Stephen Maren,et al.  Overtraining Does Not Mitigate Contextual Fear Conditioning Deficits Produced by Neurotoxic Lesions of the Basolateral Amygdala , 1998, The Journal of Neuroscience.

[36]  Response characteristics of neurons in the medial component of the medial geniculate nucleus during Pavlovian differential fear conditioning in rabbits. , 1989, Behavioral neuroscience.

[37]  Stephen Maren,et al.  A role for amygdaloid PKA and PKC in the acquisition of long-term conditional fear memories in rats , 2000, Behavioural Brain Research.

[38]  I. Geller,et al.  Subcortical mechanisms in emotional behavior; the effect of rhinencephalic injury upon the acquisition and retention of a conditioned avoidance response in cats. , 1954, Journal of comparative and physiological psychology.

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

[40]  M. Gabriel,et al.  Amygdalar Lesions Block Discriminative Avoidance Learning and Cingulothalamic Training-Induced Neuronal Plasticity in Rabbits , 1997, The Journal of Neuroscience.

[41]  Joseph E LeDoux,et al.  Is it time to invoke multiple fear learning systems in the amygdala? , 1997, Trends in Cognitive Sciences.

[42]  Hongjoo J. Lee,et al.  Amygdalar NMDA Receptors are Critical for New Fear Learning in Previously Fear-Conditioned Rats , 1998, The Journal of Neuroscience.

[43]  N. Weinberger Learning-induced changes of auditory receptive fields , 1993, Current Opinion in Neurobiology.

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

[45]  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.

[46]  Stephen Maren Neurotoxic Basolateral Amygdala Lesions Impair Learning and Memory But Not the Performance of Conditional Fear in Rats , 1999, The Journal of Neuroscience.