scholarly journals Fear Memory

2016 ◽  
Vol 96 (2) ◽  
pp. 695-750 ◽  
Author(s):  
Ivan Izquierdo ◽  
Cristiane R. G. Furini ◽  
Jociane C. Myskiw
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Inhibitory Avoidance ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Contextual Fear Conditioning ◽  
Fear Learning ◽  
Term Potentiation ◽  
Mechanisms Of Memory

Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.

scholarly journals Fear conditioning and the basolateral amygdala

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 53 ◽  
Author(s):  
Yajie Sun ◽  
Helen Gooch ◽  
Pankaj Sah
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Neural Circuits ◽  
Long Term Potentiation ◽  
Fear Learning ◽  
Pavlovian Fear Conditioning ◽  
Defensive Responses ◽  
Laboratory Rodents ◽  
Term Potentiation

Fear is a response to impending threat that prepares a subject to make appropriate defensive responses, whether to freeze, fight, or flee to safety. The neural circuits that underpin how subjects learn about cues that signal threat, and make defensive responses, have been studied using Pavlovian fear conditioning in laboratory rodents as well as humans. These studies have established the amygdala as a key player in the circuits that process fear and led to a model where fear learning results from long-term potentiation of inputs that convey information about the conditioned stimulus to the amygdala. In this review, we describe the circuits in the basolateral amygdala that mediate fear learning and its expression as the conditioned response. We argue that while the evidence linking synaptic plasticity in the basolateral amygdala to fear learning is strong, there is still no mechanism that fully explains the changes that underpin fear conditioning.

Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits

2013 ◽  
Vol 109 (5) ◽  
pp. 1391-1402 ◽  
Author(s):  
Andrew J. Delaney ◽  
Petra L. Sedlak ◽  
Elenora Autuori ◽  
John M. Power ◽  
Pankaj Sah
Keyword(s):  
Nmda Receptors ◽  
Basolateral Amygdala ◽  
Physiological Role ◽  
Long Term Potentiation ◽  
Subunit Composition ◽  
Fear Learning ◽  
Term Potentiation ◽  
Nmda Current ◽  
Synaptic Receptors ◽  
Kinetics Of

N-methyl-d-aspartate (NMDA) receptors are heteromultimeric ion channels that contain an essential GluN1 subunit and two or more GluN2 (GluN2A–GluN2D) subunits. The biophysical properties and physiological roles of synaptic NMDA receptors are dependent on their subunit composition. In the basolateral amygdala (BLA), it has been suggested that the plasticity that underlies fear learning requires activation of heterodimeric receptors composed of GluN1/GluN2B subunits. In this study, we investigated the subunit composition of NMDA receptors present at synapses on principal neurons in the BLA. Purification of the synaptic fraction showed that both GluN2A and GluN2B subunits are present at synapses, and co-immunoprecipitation revealed the presence of receptors containing both GluN2A and GluN2B subunits. The kinetics of NMDA receptor-mediated synaptic currents and pharmacological blockade indicate that heterodimeric GluN1/GluN2B receptors are unlikely to be present at glutamatergic synapses on BLA principal neurons. Selective RNA interference-mediated knockdown of GluN2A subunits converted synaptic receptors to a GluN1/GluN2B phenotype, whereas knockdown of GluN2B subunits had no effect on the kinetics of the synaptically evoked NMDA current. Blockade of GluN1/GluN2B heterodimers with ifenprodil had no effect, but knockdown of GluN2B disrupted the induction of CaMKII-dependent long-term potentiation at these synapses. These results suggest that, on BLA principal neurons, GluN2B subunits are only present as GluN1/GluN2A/GluN2B heterotrimeric NMDA receptors. The GluN2B subunit has little impact on the kinetics of the receptor, but is essential for the recruitment of signaling molecules essential for synaptic plasticity.

Isoflurane Impairs Learning and Hippocampal Long-term Potentiation via the Saturation of Synaptic Plasticity

2014 ◽  
Vol 121 (2) ◽  
pp. 302-310 ◽  
Author(s):  
Kazuhiro Uchimoto ◽  
Tomoyuki Miyazaki ◽  
Yoshinori Kamiya ◽  
Takahiro Mihara ◽  
Yukihide Koyama ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Western Blotting ◽  
Field Potential ◽  
Inhibitory Avoidance ◽  
Long Term Potentiation ◽  
Fear Learning ◽  
Male Rats ◽  
Avoidance Task ◽  
Term Potentiation

Abstract Background: General anesthesia induces long-lasting cognitive and learning deficits. However, the underlying mechanism remains unknown. The GluA1 subunit of AMPAR is a key molecule for learning and synaptic plasticity, which requires trafficking of GluA1-containing AMPARs into the synapse. Methods: Adult male rats were exposed to 1.8% isoflurane for 2 h and subjected to an inhibitory avoidance task, which is a hippocampus-dependent contextual fear learning paradigm (n = 16 to 39). The in vitro extracellular field potential of hippocampal synapses between the Schaffer collateral and the CA1 was evaluated using a multielectrode recorder (n = 6 per group). GluA1 expression in the synaptoneurosome was assessed using Western blotting (n = 5 to 8). The ubiquitination level of GluA1 was evaluated using immunoprecipitation and Western blotting (n = 7 per group). Results: Seven days after exposure to 1.8% isoflurane for 2 h (Iso1.8), the inhibitory avoidance learning (control vs. Iso1.8; 294 ± 34 vs. 138 ± 28, the mean ± SEM [%]; P = 0.002) and long-term potentiation (125.7 ± 6.1 vs. 105.7 ± 3.3; P < 0.001) were impaired. Iso1.8 also temporarily increased GluA1 in the synaptoneurosomes (100 ± 9.7 vs. 138.9 ± 8.9; P = 0.012) and reduced the GluA1 ubiquitination, a main degradation pathway of GluA1 (100 ± 8.7 vs. 71.1 ± 6.1; P = 0.014). Conclusions: Isoflurane impairs hippocampal learning and modulates synaptic plasticity in the postanesthetic period. Increased GluA1 may reduce synaptic capacity for additional GluA1-containing AMPARs trafficking.

scholarly journals CaMKII binding to GluN2B is important for massed spatial learning in the Morris water maze

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 193 ◽  
Author(s):  
Ivar S. Stein ◽  
Michaela S. Donaldson ◽  
Johannes W. Hell
Keyword(s):  
Fear Conditioning ◽  
Morris Water Maze ◽  
Water Maze ◽  
Specific Interaction ◽  
Long Term Potentiation ◽  
Contextual Fear Conditioning ◽  
Barnes Maze ◽  
Contextual Fear ◽  
Term Potentiation ◽  
Dependent Protein

Learning and memory as well as long-term potentiation (LTP) depend on Ca2+ influx through the NMDA-type glutamate receptor (NMDAR) and the resulting activation of the Ca2+ and calmodulin-dependent protein kinase (CaMKII). Ca2+ influx via the NMDAR triggers CaMKII binding to the NMDAR for enhanced CaMKII accumulation at post-synaptic sites that experience heightened activity as occurring during LTP. Previously, we generated knock-in (KI) mice in which we replaced two residues in the NMDAR GluN2B subunit to impair CaMKII binding to GluN2B. Various forms of LTP at the Schaffer collateral synapses in CA1 are reduced by 50%. Nevertheless, working memory in the win-shift 8 arm maze and learning of the Morris water maze (MWM) task was normal in the KI mice although recall of the task was impaired in these mice during the period of early memory consolidation. We now show that massed training in the MWM task within a single day resulted in impaired learning. However, learning and recall of the Barnes maze task and contextual fear conditioning over one or multiple days were surprisingly unaffected. The differences observed in the MWM compared to the Barnes maze and contextual fear conditioning suggest a differential involvement of CaMKII and the specific interaction with GluN2B, probably depending on varying degrees of stress, cognitive demand or even potentially different plasticity mechanisms associated with the diverse tasks.

scholarly journals Involvement of Cerebellum in Emotional Behavior

2011 ◽  
pp. S39-S48 ◽  
Author(s):  
P. STRATA ◽  
B. SCELFO ◽  
B. SACCHETTI
Keyword(s):  
Long Term Potentiation ◽  
Fear Memory ◽  
Emotional Behavior ◽  
Fear Learning ◽  
Inhibitory Synapses ◽  
Reversible Inactivation ◽  
Sensory Stimuli ◽  
Term Potentiation ◽  
Reported Data

In the last decade a growing body of data revealed that the cerebellum is involved in the regulation of the affective reactions as well as in forming the association between sensory stimuli and their emotional values. In humans, cerebellar areas around the vermis are activated during mental recall of emotional personal episodes and during learning of a CS-US association. Lesions of the cerebellar vermis may affect retention of a fear memory without altering baseline motor/autonomic responses to the frightening stimuli in both human and animal models. Reversible inactivation of the vermis during the consolidation period impairs retention of fear memory in rodents. Recent findings demonstrate that long-term potentiation (LTP) of synapses in the cerebellar cortex occurs in relation to associative fear learning similar to previously reported data in the hippocampus and amygdala. Plastic changes affect both excitatory and inhibitory synapses. This concomitant potentiation allows the cerebellar cortical network to detect coincident inputs, presumably conveying sensorial stimuli, with better efficacy by keeping the time resolution of the system unchanged. Collectively, these data suggest that the vermis participates in forming new CS-US association and translate an emotional state elaborated elsewhere into autonomic and motor responses.

Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake

10.1038/nn791 ◽  
2002 ◽  
Vol 5 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Jonathan Levenson ◽  
Edwin Weeber ◽  
Joel C. Selcher ◽  
Lorna S. Kategaya ◽  
J. David Sweatt ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Glutamate Uptake ◽  
Long Term Potentiation ◽  
Contextual Fear Conditioning ◽  
Contextual Fear ◽  
Term Potentiation

scholarly journals Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress

2017 ◽  
Author(s):  
Ran Inoue ◽  
Kareem Abdou ◽  
Ayumi Hayashi-Tanaka ◽  
Shin-ichi Muramatsu ◽  
Kaori Mino ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Fear Conditioning ◽  
Adaptive Modulation ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Suppressive Effect ◽  
Dependent Manner ◽  
Term Potentiation ◽  
Lateral Nucleus

AbstractGlucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions.

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