Potentiated amygdaloid auditory-evoked potentials and freezing behavior after fear conditioning in mice

Elucidation of cellular and molecular mechanisms underlying fear-related memory would greatly benefit from the possibility of combined behavioral and electrophysiological recordings in genetically modified mice. As a first step to this goal, we implanted adult C57BL/6J mice with recording electrodes aimed at the basolateral amygdaloid complex and trained them in an auditory fear conditioning paradigm. After conditioning, animals with paired tone and footshock presentation showed not only intensified freezing behavior lasting for 2 days, but also increases, lasting 4 days, in slope and amplitude of the most negative component of auditory-evoked potentials triggered by the conditioned stimulus. These effects could not be observed in animals with unpaired tone and footshock presentation. Thus, our data show that a long-lasting association of a former neutral tone with an aversive situation is accompanied by a long-lasting increase of auditory-evoked potentials in freely moving mice. However, extinction of the potentiation of auditory-evoked potentials and freezing behavior followed different time courses, thus making a direct relationship between these responses unlikely.

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

[2]  O. Stiedl,et al.  Effect of tone-dependent fear conditioning on heart rate and behavior of C57BL/6N mice. , 1997, Behavioral neuroscience.

[3]  R. Gerlai.  Contextual learning and cue association in fear conditioning in mice: a strain comparison and a lesion study , 1998, Behavioural Brain Research.

[4]  S. Grant,et al.  A role for the Ras signalling pathway in synaptic transmission and long-term memory , 1997, Nature.

[5]  Joseph E LeDoux,et al.  Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA, and MAP kinase. , 1999, Learning & memory.

[6]  M. Picciotto,et al.  Using knockout and transgenic mice to study neurophysiology and behavior. , 1998, Physiological reviews.

[7]  M. Fendt,et al.  The neuroanatomical and neurochemical basis of conditioned fear , 1999, Neuroscience & Biobehavioral Reviews.

[8]  Norman M. Weinberger,et al.  Sensitization induced receptive field plasticity in the auditory cortex is independent of CS-modality , 1992, Brain Research.

[9]  T. Bliss,et al.  Induction and duration of long-term potentiation in the hippocampus of the freely moving mouse , 1997, Journal of Neuroscience Methods.

[10]  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.

[11]  Graham L. Collingridge,et al.  The LTP Program: a data acquisition program for on-line analysis of long-term potentiation and other synaptic events , 2001, Journal of Neuroscience Methods.

[12]  Joseph E LeDoux.  Fear and the brain: where have we been, and where are we going? , 1998, Biological Psychiatry.

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

[14]  Norman M. Weinberger,et al.  Learning-Induced Receptive Field Plasticity in the Primary Auditory Cortex , 1997 .

[15]  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.

[16]  Joseph E. LeDoux,et al.  LTP is accompanied by commensurate enhancement of auditory-evoked responses in a fear conditioning circuit , 1995, Neuron.

[17]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

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

[19]  J. Edeline.  Learning-induced physiological plasticity in the thalamo-cortical sensory systems: a critical evaluation of receptive field plasticity, map changes and their potential mechanisms , 1999, Progress in Neurobiology.

[20]  R Jaffard,et al.  Footshock stress but not contextual fear conditioning induces long‐term enhancement of auditory‐evoked potentials in the basolateral amygdala of the freely behaving rat , 1998, The European journal of neuroscience.

[21]  M. Fanselow,et al.  Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala. , 1994, Behavioral neuroscience.

[22]  C. Stevens,et al.  A Million Dollar Question: Does LTP = Memory? , 1998, Neuron.

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

[24]  N. Schneiderman,et al.  Changes of synaptic efficacy in the medial geniculate nucleus as a result of auditory classical conditioning , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[26]  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.

[27]  Norman M. Weinberger,et al.  Classical conditioning induces CS-specific receptive field plasticity in the auditory cortex of the guinea pig , 1990, Brain Research.

[28]  Alcino J. Silva,et al.  Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein , 1994, Cell.

[29]  P Andersen,et al.  Brain temperature and hippocampal function , 1995, Hippocampus.

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

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