The neuroanatomical and neurochemical basis of conditioned fear
Neuroscience & Biobehavioral ReviewsPublished 1 May 1999
Markus Fendt, Michael S. Fanselow
Citations1,096
SJR quartileQ1
SJR score3.08
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TL;DR
The present review summarizes and compares the results of different laboratories investigating the neuroanatomical and neurochemical basis of conditioned fear, focusing primarily on the behavioral models of freezing and fear-potentiated startle in rats and describes the pathways mediating and modulating fear.
Abstract
After a few pairings of a threatening stimulus with a formerly neutral cue, animals and humans will experience a state of conditioned fear when only the cue is present. Conditioned fear provides a critical survival-related function in the face of threat by activating a range of protective behaviors. The present review summarizes and compares the results of different laboratories investigating the neuroanatomical and neurochemical basis of conditioned fear, focusing primarily on the behavioral models of freezing and fear-potentiated startle in rats. On the basis of these studies, we describe the pathways mediating and modulating fear. We identify several key unanswered questions and discuss possible implications for the understanding of human anxiety disorders.
Keywords
Neuroscience
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The fear-potentiated startle paradigm was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5), suggesting that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities.
NatureSecond-order fear conditioning prevented by blocking NMDA receptors in amygdala
253 Citations1997Jonathan C. Gewirtz, Michael T. Davis
It is reported here that intra-amygdala AP5 actually enhances expression of conditioned fear to the conditioned stimulus that provides the reinforcement signal for second-order conditioning, which strongly support the view that NMDA receptors are critically involved in synaptic plasticity.
Annual Review of PsychologyMammalian Brain Substrates of Aversive Classical Conditioning
249 Citations1993David G. Lavond, Jeansok J. Kim +1 more
This review has examined recent studies that have successfully identified neural circuits necessary for nonspecific and specific conditioned responses and demonstrated the power of the classical conditioning paradigm for controlling stimuli and responses.
PubMedThe elevated T maze, a new experimental model of anxiety and memory: effect of diazepam.
247 Citations1993Frederico Guilherme Graeff, Milena de Barros Viana +1 more
The view that the anxiolytic and amnestic effects of benzodiazepines are closely related is supported, and this new elevated T maze model may be useful for simultaneous measurement of drug effects on anxiety and memory is suggested.
Behavioral NeuroscienceEffects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats.
242 Citations1994Fred J. Helmstetter, Patrick S.F. Bellgowan
Results indicate that acquisition-related processes that may be occurring within the amygdala are more difficult to disrupt than those associated with performance.
Brain ResearchMesencephalic central gray lesions and fear-motivated behavior in rats
240 Citations1970Jeffrey M. Liebman, David Mayer +1 more
It was concluded that the mesencephalic central gray matter, and in particular its ventrolateral aspect, is critical to the normal expression of fear in rats.
Neurobiology of Learning and MemoryNorepinephrine Release in the Amygdala in Response to Footshock Stimulation
235 Citations1996Roberto Galvez, Michael H. Mesches +1 more
In both groups, the footshock stimulation increased NE levels to approximately 75% above basal levels in the first sample collected after the foot shock and the levels returned to baseline within 30 min.
SynapseLong‐Term synaptic potentiation in the amygdala
230 Citations1990Paul F. Chapman, Edward W. Kairiss +2 more
In vitro methods and results that may help elucidate cellular learning mechanisms in amygdala neurons are reported, finding that high‐frequency stimulation of the EC induced LTP in 80% of the cells from which suitable recordings were obtained.
Behavioral NeuroscienceSensitization of the acoustic startle reflex by footshock.
228 Citations1989Michael T. Davis
Footshocks increased startle in rats not previously given startle-eliciting stimuli, indicating sensitization rather than dishabituation, and may represent the unconditioned effect of shock that can become associated with a neutral stimulus to support classical fear conditioning.
Brain ResearchNorepinephrine release in the amygdala in response to footshock and opioid peptidergic drugs
226 Citations1998Gina L. Quirarte, Roberto Galvez +2 more
The findings are consistent with previous evidence that acute, mildly stressful stimulation induces the release of NE in the amygdala as well as with extensive pharmacological evidence indicating that amygdala NE released by arousing stimulation is involved in regulating memory storage and that the opioid peptidergic system influences memory storage by modulating the release from the amygdala.
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