A thalamo-amygdalar circuit underlying the extinction of remote fear memories

Silva, Bianca A.; Astori, Simone; Burns, Allison M.; Heiser, Hendrik; Heuvel, L. van den; Santoni, Giulia; Martinez-Reza, Maria Fernanda; Sandi, Carmen; Gräff, Johannes

doi:10.1038/s41593-021-00856-y

Cited by 64 publications

(55 citation statements)

References 79 publications

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“…IL projections to the HPC via the thalamic nucleus reuniens are also critical for extinction learning and retrieval ( Ramanathan et al, 2018 ; Ramanathan and Maren, 2019 ). In turn, reciprocal projections within these networks are involved in extinction retrieval and the suppressing of conditional responding ( Senn et al, 2014 ; Jin and Maren, 2015 ; Marek et al, 2018 ; Silva et al, 2021 ).…”

Section: Stress Modulates Neural Circuits Critical For Extinction Lea...mentioning

confidence: 99%

Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit

Maren

2022

Front. Syst. Neurosci.

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Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortunately, fear memories are durable, long-lasting, and resistant to extinction, particularly under high levels of stress. This is illustrated by the “immediate extinction deficit,” which is characterized by a poor long-term reduction of conditioned fear when extinction procedures are attempted within hours of fear conditioning. Here, I will review recent work that has provided new insight into the neural mechanisms underlying resistance to fear extinction. Emerging studies reveal that locus coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are critical for extinction learning. These data suggest that stress-induced activation of brain neuromodulatory systems biases fear memory at the expense of extinction learning. Behavioral and pharmacological strategies to reduce stress in patients undergoing exposure therapy might improve therapeutic outcomes.

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Section: Stress Modulates Neural Circuits Critical For Extinction Lea...mentioning

confidence: 99%

Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit

Maren

2022

Front. Syst. Neurosci.

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“…That could be a psychological effect when participants observe their hand movement without pain during rPMS-generated muscle contraction. However, this could be also related to the activation of thalamo-amygdala circuits, which were recently revealed as attenuators of remote fear memories in mice ( 76 ). Indeed, rPMS activates the lemniscal pathway (as evidenced by proprioceptive magnetic SEP), thus the thalamus is recruited and such circuits of fear attenuation could be involved in the long-term changes observed in the present study.…”

Section: Discussionmentioning

confidence: 97%

Theta-Burst Stimulation of Forearm Muscles in Patients With Complex Regional Pain Syndrome: Influence on Brain and Clinical Outcomes

2021

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Objective: Complex regional pain syndrome (CRPS) is a common pain condition characterized by the changes in the brain that are not yet addressed by conventional treatment regimens. Repetitive peripheral magnetic stimulation (rPMS) of muscles is painless and non-invasive and can influence these changes (the induction of brain plasticity) to reduce pain and improve motricity. In patients with CRPS, this open-label pilot study tested rPMS after-effects on the pain intensity and sensorimotor control of the upper limb along with the excitability changes of the primary motor cortex (M1).Methods: Eight patients with CRPS were enrolled in a single-session program. Patients were tested at pre- and post-rPMS over the flexor digitorum superficialis (FDS) muscle. The clinical outcomes were pain intensity, proprioception, active range of motion (ROM), and grip strength. M1 excitability was tested using the single- and paired-pulse transcranial magnetic stimulation (TMS) of M1.Results: In our small sample study, rPMS reduced instant and week pain, improved proprioception and ROM, and reduced the hemispheric imbalance of several TMS outcomes. The more M1 contralateral to the CRPS side was hyperactivated at baseline, the more pain was reduced.Discussion: This open-label pilot study provided promising findings for the use of rPMS in CRPS with a focus on M1 plastic changes. Future randomized, placebo-controlled clinical trials should confirm the existence of a causal relationship between the TMS outcomes and post-rPMS decrease of pain. This will favor the development of personalized treatments of peripheral non-invasive neurostimulation in CRPS.

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“…Previous evidence in the literature shows that biological relevant stimuli (such as fear), complex tasks and fear memory extinction [17][18][19][20][21][22] all lead to RE activation, which regulates learning and memory consolidation when the interaction between the prefrontal cortex and the dHP is required [23][24][25] . Our findings add to this body of data, showing that the RE activation is also determined by information load and that its level of activation is tuned differently in the two sexes.…”

Section: Discussionmentioning

confidence: 99%

Thalamo-hippocampal pathway regulates incidental memory load in mice

Torromino

Loffredo

Cavezza

et al. 2021

Preprint

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Memory can be challenged by increasing both its required duration and the amount of information to be encoded, namely the memory load. The dorsal hippocampus (dHP) has been involved in memory consolidation, which is the stabilization of a trace from short-term (STM) to long-term memory (LTM), as well as in the ability to process high information load. However, how memory load influences memory consolidation, and the underlying neural mechanisms, are yet unknown. To address this question, we used male and female mice that, despite having in our Different Object recognition Task (DOT) the same STM capacity of 6 objects, spontaneously show differences in the number of objects directly transferred to LTM, when tested over longer delays. Males memorize all 6 objects encoded, while females remember only up to 4, both at 1 and 24 h delays. Interestingly, males activate more the dHP (as measured by c-Fos expression), while females the thalamic nucleus reuniens (RE). Optogenetic inhibition of the RE-dHP pathway during off-line memory consolidation favors 6-object LTM retention in females by removing inhibitory control over dHP activation, while chemogenetic RE-activation impairs it in males. Our data represent a first demonstration of a sub-cortical control of dHP recruitment, that might underlie its sex-dependent activation during incidental memory, with potential also for clinical application.

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A thalamo-amygdalar circuit underlying the extinction of remote fear memories

Cited by 64 publications

References 79 publications

Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit

Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit

Theta-Burst Stimulation of Forearm Muscles in Patients With Complex Regional Pain Syndrome: Influence on Brain and Clinical Outcomes

Thalamo-hippocampal pathway regulates incidental memory load in mice

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