Long-term potentiation in the amygdala: A cellular mechanism of fear learning and memory
Section snippets
Introduction: A cellular hypothesis of fear conditioning
Long-term potentiation (LTP) has received a tremendous amount of attention in the roughly 30 years since it was first described by Bliss and Lomo (1973). This interest has been fueled to a large degree by the widely held hypothesis that learning and memory is mediated by changes in the strength of synapses in neural circuits. According to this hypothesis, neural activity during learning gives rise to long-term changes in synaptic strength, which allows memories to be stored and later retrieved (
CS-evoked responses in the LA increase during fear conditioning
If fear conditioning is mediated by an increase in the strength of synapses that carry auditory (CS) information to the LA, one would expect to observe an enhancement in the responses of LA neurons to a CS during the course of fear learning. To date, this prediction has been confirmed by a number of studies that have recorded either field potential or single-unit responses in the LA during fear conditioning (Quirk et al., 1995, Rogan et al., 1997, Collins and Pare, 2000, Repa et al., 2001,
Outstanding questions for future research
Although considerable progress has been made in relating synaptic plasticity in the amygdala to fear learning and memory, several questions concerning this relationship remain unanswered. Below we discuss three research questions that may advance our understanding of how plasticity in the LA contributes to fear conditioning in the coming years. This list is not meant to be exhaustive, but rather to highlight a few important outstanding questions.
Conclusion
Considerable progress has been made in relating activity-dependent changes in synaptic strength to learning and memory since Bliss and Lomo first described LTP in 1973. We have argued that studies linking fear conditioning to LTP in the amygdala constitute an important part of this progress. The findings reviewed here strongly suggest that LTP-like synaptic changes occur as a result of fear learning, and that such changes are necessary for fear memories to be formed. Nevertheless, our
Acknowledgments
This work was supported by NIH Grants R01 MH46516, R37 MH38774, K05 MH067048, and P50 MH58911 to J.E.L., an NIMH NRSA MH077458 to C.K.C. and CNRS-PICS to V.D.
References (133)
Fear extinction in rodents: basic insight to clinical promise
Curr. Opin. Neurobiol.
(2005)Involvement of LTP in memory: are we “searching under the street light”?
Neuron
(1995)- et al.
Evidence that dopaminergic axons provide a dense innervation of specific neuronal subpopulations in the rat basolateral amygdala
Brain Res.
(1999) - et al.
Is the amygdala a locus of “conditioned fear”? Some questions and caveats
Neuron
(1999) - et al.
Finding the intracellular signaling pathways affected by mood disorder treatments
Neuron
(2003) - et al.
Auditory-evoked spike firing in the lateral amygdala and Pavlovian fear conditioning: mnemonic code or fear bias?
Neuron
(2003) - et al.
Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning measured with fear-potentiated startle
Brain Res.
(2001) - et al.
Amygdaloid D1 dopamine receptor involvement in Pavlovian fear conditioning
Brain Res.
(1999) - et al.
Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala
Neuron
(1998) - et al.
Dendritic spine heterogeneity determines afferent-specific Hebbian plasticity in the amygdala
Neuron
(2005)
Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala
Neuroscience
Overlapping projections to the amygdala and striatum from auditory processing areas of the thalamus and cortex
Neurosci. Lett.
LTP and LTD: an embarrassment of riches
Neuron
A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function
Neuron
Corticoamygdaloid and corticocortical projections of the rat temporal cortex: a Phaseolus vulgaris leucoagglutinin study
Neuroscience
Cortical pathways to the mammalian amygdala
Prog. Neurobiol.
Localization of GABA-like immunoreactivity in the monkey amygdala
Neuroscience
Localization of the CB1 type cannabinoid receptor in the rat basolateral amygdala: high concentrations in a subpopulation of cholecystokinin-containing interneurons
Neuroscience
Behavioral and neural analysis of extinction
Neuron
Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat
Neuron
Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala
Neuron
Molecular mechanisms underlying emotional learning and memory in the lateral amygdala
Neuron
LTP is accompanied by commensurate enhancement of auditory-evoked responses in a fear conditioning circuit
Neuron
Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse
Neuron
Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus
Nat. Neurosci.
Lesions of the basal amygdala block expression of conditioned fear but not extinction
J. Neurosci.
Auditory fear conditioning and long-term potentiation in the lateral amygdala require ERK/MAP kinase signaling in the auditory thalamus: a role for presynaptic plasticity in the fear system
J. Neurosci.
Differential effects of amygdala lesions on early and late plastic components of auditory cortex spike trains during fear conditioning
J. Neurosci.
Heterosynaptic long-term potentiation of inhibitory interneurons in the lateral amygdala
J. Neurosci.
Fear conditioning and LTP in the lateral amygdala are sensitive to the same stimulus contingencies
Nat. Neurosci.
NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala
J. Neurosci.
Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition
Nat. Neurosci.
Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning
Learn. Mem.
Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path
J. Physiol.
A synaptic model of memory: long-term potentiation in the hippocampus
Nature
Stress impairs alpha(1A) adrenoceptor-mediated noradrenergic facilitation of GABAergic transmission in the basolateral amygdala
Neuropsychopharmacology
The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice
Learn. Mem.
Involvement of subcortical and cortical afferents to the lateral nucleus of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli
J. Neurosci.
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
J. Neurosci.
Intra-amygdala infusion of the N-methyl-d-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus
Behav. Neurosci.
Induction of long-term potentiation in the basolateral amygdala does not depend on NMDA receptor activation
Synapse
Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear
Neuropsychopharmacology
Synaptic plasticity in fear conditioning circuits: induction of LTP in the lateral nucleus of the amygdala by stimulation of the medial geniculate body
J. Neurosci.
Differential fear conditioning induces reciprocal changes in the sensory responses of lateral amygdala neurons to the CS(+) and CS(−)
Learn. Mem.
The role of the amygdala in conditioned and unconditioned fear and anxiety
Role of NMDA receptors and MAP kinase in the amygdala in extinction of fear: clinical implications for exposure therapy
Eur. J. Neurosci.
Cells in the posterior thalamus project to both amygdala and temporal cortex: a quantitative retrograde double-labeling study in the rat
J. Comp. Neurol.
Long-term potentiation in freely moving rats reveals asymmetries in thalamic and cortical inputs to the lateral amygdala
Eur. J. Neurosci.
Spatial learning. The LTP-memory connection
Nature
Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats
Learn. Mem.
Cited by (251)
Presynaptic HCN channel activity is required for the expression of long-term potentiation at lateral amygdala to basal amygdala synapses
2022, Biochemical and Biophysical Research CommunicationsAuditory fear conditioning facilitates neurotransmitter release at lateral amygdala to basal amygdala synapses
2021, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The LA is a main input station of the amygdala and receives the sensory information. The LA is thought to encode and maintains the sensory associations as a form of LTP [5,8,9]. Many studies revealed that plastic change in the intra-amygdaloid pathways is more distributed than previously appreciated [19].
Pharmacological rewriting of fear memories: A beacon for post-traumatic stress disorder
2020, European Journal of PharmacologyAdenosine and Cortical Plasticity
2024, Neuroscientist