Encoding of fear learning and memory in distributed neuronal circuits

Herry, Cyril; Johansen, Joshua P.

doi:10.1038/nn.3869

Cited by 417 publications

(383 citation statements)

References 119 publications

(167 reference statements)

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“…The activity of BLA neurons is not exclusively shaped by sensory input, however; principal neurons and interneurons in the BLA have been shown to receive monosynaptic input from mPFC and vHPC, and send reciprocal projections to both of these regions [66][67][68] . Activity within these pathways can both directly invigorate the anxiety response (e.g., through projections of the vHPC to the lateral septum and hypothalamic nuclei; see below), as well as influence the likelihood of a threat appraisal (e.g., through fear memory retrieval via mPFC projections to the amygdala; see below, and 69 ).…”

Section: Interpreting Threats On the Macrocircuit Levelmentioning

confidence: 99%

Resolving the neural circuits of anxiety

2015

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Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with absolute certainty the subjective experience of a rodent, rodent models hold promise in dissecting wellconserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety, and thereby provides a roadmap for future therapeutic development.3

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Section: Interpreting Threats On the Macrocircuit Levelmentioning

confidence: 99%

Resolving the neural circuits of anxiety

2015

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“…From a neurobiological perspective, a pivotal mechanism for transforming threat into adaptive behaviors is Pavlovian fear conditioning, a form of associative learning that allows to predict aversive events (Herry and Johansen, 2014). Experimentally, Pavlovian fear conditioning is established by repeatedly coupling a neutral stimulus (CS+) with an aversive stimulus (UCS), which leads to a conditioned response (CR) to the CS+ alone (Sehlmeyer et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Studies of intranasally delivered exogenous OXT (OXT IN ) have shown that the peptide produces anxiolytic-like effects as a result of dampened amygdala reactivity to threat (Eckstein and Hurlemann, 2013;Domes et al, 2007, but see Lischke et al, 2012), thereby promoting in-group trust (Kosfeld et al, 2005), cooperation (De Dreu et al, 2010) and affiliative behaviors (Hurlemann and Scheele, 2015;Rilling and Young, 2014). The amygdala-an ensemble of functionally distinct nuclei located in the medial temporal lobe-is central to a distributed neural circuitry orchestrating Pavlovian fear conditioning in humans and other species, underscoring its crucial role in promoting reproductive fitness (Herry and Johansen, 2014).…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Facilitates Pavlovian Fear Learning in Males

Eckstein

Scheele

Patin

et al. 2015

Neuropsychopharmacol

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In human evolution, social group living and Pavlovian fear conditioning have evolved as adaptive mechanisms promoting survival and reproductive success. The evolutionarily conserved hypothalamic peptide oxytocin is a key modulator of human sociality, but its effects on fear conditioning are still elusive. In the present randomized controlled study involving 97 healthy male subjects, we therefore employed functional magnetic resonance imaging and simultaneous skin conductance response (SCR) measures to characterize the modulatory influence of intranasal oxytocin (24 IU) on Pavlovian fear conditioning. We found that the peptide strengthened conditioning on both the behavioral and neural levels. Specifically, subjects exhibited faster task-related responses and enhanced SCRs to fear-associated stimuli in the late phase of conditioning, which was paralleled by heightened activity in cingulate cortex subregions in the absence of changes in amygdala function. This speaks against amygdalocentric views of oxytocin having pure anxiolytic-like effects. Instead, it suggests that the peptide enables extremely rapid and flexible adaptation to fear signals in social contexts, which may confer clear evolutionary advantages but could also elevate vulnerability for the pathological sequelae of interpersonal trauma.

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“…Pavlovian auditory threat (fear) conditioning (23, 24) is a form of associative learning during which a neutral auditory conditioned stimulus (CS) is temporally paired with an aversive unconditioned stimulus (US), often a mild electric shock (17,20,21,(25)(26)(27). Following training, the auditory CS comes to elicit behavioral defense responses (such as freezing) and supporting physiological changes controlled by the autonomic nervous and endocrine systems.…”

mentioning

confidence: 99%

Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation

Johansen

Díaz-Mataix

Hamanaka

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

168

138

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A long-standing hypothesis termed "Hebbian plasticity" suggests that memories are formed through strengthening of synaptic connections between neurons with correlated activity. In contrast, other theories propose that coactivation of Hebbian and neuromodulatory processes produce the synaptic strengthening that underlies memory formation. Using optogenetics we directly tested whether Hebbian plasticity alone is both necessary and sufficient to produce physiological changes mediating actual memory formation in behaving animals. Our previous work with this method suggested that Hebbian mechanisms are sufficient to produce aversive associative learning under artificial conditions involving strong, iterative training. Here we systematically tested whether Hebbian mechanisms are necessary and sufficient to produce associative learning under more moderate training conditions that are similar to those that occur in daily life. We measured neural plasticity in the lateral amygdala, a brain region important for associative memory storage about danger. Our findings provide evidence that Hebbian mechanisms are necessary to produce neural plasticity in the lateral amygdala and behavioral memory formation. However, under these conditions Hebbian mechanisms alone were not sufficient to produce these physiological and behavioral effects unless neuromodulatory systems were coactivated. These results provide insight into how aversive experiences trigger memories and suggest that combined Hebbian and neuromodulatory processes interact to engage associative aversive learning.Hebbian plasticity | amygdala | neuromodulation | instructive signals | associative learning H ebbian plasticity refers to the strengthening of a presynaptic input onto a postsynaptic neuron when both pre-and postsynaptic neurons are coactive (1). This was originally proposed as a mechanism for memory formation. Findings from in vitro and in vivo physiological studies suggest that Hebbian processes control synaptic strengthening (2-10). However, other results and theories suggest that Hebbian mechanisms alone are not normally sufficient for producing synaptic plasticity and that synaptic strengthening mediating memory formation involves interactions between Hebbian and neuromodulatory mechanisms (3,4,7,(11)(12)(13)(14)(15)(16)(17)(18)(19). Although molecules that may mediate Hebbian processes in memory formation have been identified (3,11,16,17,(20)(21)(22), it has been difficult to directly test whether Hebbian plasticity alone or in combination with neuromodulation is necessary and sufficient to produce neural plasticity and memories in behaving animals (especially in mammals). This is because of technical limitations in controlling correlated activity between pre-and postsynaptic neurons involved in memory storage in a temporally/spatially precise manner while measuring behavioral memory formation and neural plasticity.To overcome these problems, we used optogenetic techniques to directly manipulate Hebbian mechanisms in pyramidal neurons in the lateral nucl...

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Encoding of fear learning and memory in distributed neuronal circuits

Cited by 417 publications

References 119 publications

Resolving the neural circuits of anxiety

Resolving the neural circuits of anxiety

Oxytocin Facilitates Pavlovian Fear Learning in Males

Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation

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