Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits

Ressler, Kerry J.; Berretta, Sabina; Bolshakov, Vadim Y.; Rosso, Isabelle M.; Meloni, Edward G.; Rauch, Scott L.; Carlezon, William A.

doi:10.1038/s41582-022-00635-8

Cited by 210 publications

(158 citation statements)

References 249 publications

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“…Extinction does not erase the fear memory (i.e., CS-US association), but rather creates a new inhibitory memory that competes with the original fear memory (Quirk and Mueller, 2008). Pavlovian fear conditioning and extinction have direct clinical relevance as the circuits that underly adaptive fear learning are thought to be disordered in patients with anxietyand trauma-based disorders, such as post-traumatic stress order (Ressler et al, 2022). Moreover, extinction learning is the basis for commonly used cognitive behavioral therapies, such as exposure therapy (Milad and Quirk, 2012;VanElzakker et al, 2014;Ressler et al, 2022).…”

Section: Behavioral Paradigms For the Study Of Fear And Anxiety In Ro...mentioning

confidence: 99%

“…This reveals that extinction learning does not result in the erasure of the original fear memory but instead forms a new memory trace that competes with and inhibits the fear memory. Importantly, extinction learning is the basis of commonly employed cognitive-behavioral therapies for reducing fear and anxiety in anxiety-and trauma-related disorders (Milad and Quirk, 2012;Ressler et al, 2022). Although the oscillatory correlates of conditioned fear have been well described, much less is known about the role for oscillations in extinction learning and retrieval (Trenado et al, 2018).…”

Section: Prefrontal Top-down Theta Synchrony Regulates Fear Extinctionmentioning

confidence: 99%

“…The dysregulation of neural circuits that guide adaptive learning and memory are thought to underlie trauma-and anxiety-related disorders (Milad and Quirk, 2012;Maren et al, 2013;Ressler et al, 2022). Activity within these brain circuits is coordinated by electrical oscillations that influence a range of neuronal processes to synchronize and modulate network function.…”

Section: Introductionmentioning

confidence: 99%

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Neural Oscillations in Aversively Motivated Behavior

Totty

Maren²

2022

Front. Behav. Neurosci.

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Fear and anxiety-based disorders are highly debilitating and among the most prevalent psychiatric disorders. These disorders are associated with abnormal network oscillations in the brain, yet a comprehensive understanding of the role of network oscillations in the regulation of aversively motivated behavior is lacking. In this review, we examine the oscillatory correlates of fear and anxiety with a particular focus on rhythms in the theta and gamma-range. First, we describe neural oscillations and their link to neural function by detailing the role of well-studied theta and gamma rhythms to spatial and memory functions of the hippocampus. We then describe how theta and gamma oscillations act to synchronize brain structures to guide adaptive fear and anxiety-like behavior. In short, that hippocampal network oscillations act to integrate spatial information with motivationally salient information from the amygdala during states of anxiety before routing this information via theta oscillations to appropriate target regions, such as the prefrontal cortex. Moreover, theta and gamma oscillations develop in the amygdala and neocortical areas during the encoding of fear memories, and interregional synchronization reflects the retrieval of both recent and remotely encoded fear memories. Finally, we argue that the thalamic nucleus reuniens represents a key node synchronizing prefrontal-hippocampal theta dynamics for the retrieval of episodic extinction memories in the hippocampus.

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Section: Behavioral Paradigms For the Study Of Fear And Anxiety In Ro...mentioning

confidence: 99%

Section: Prefrontal Top-down Theta Synchrony Regulates Fear Extinctionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neural Oscillations in Aversively Motivated Behavior

Totty

Maren²

2022

Front. Behav. Neurosci.

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“…The PTSD provides an exemplificative case of a dramatic alteration of the adaptive physiological nature of the body-brain system. The traumatic experience, when inducing dysregulation of neuronal, hormonal, and immune mechanisms (Ressler et al, 2022 ) can result in a psychopathological condition characterized by altered adaptive behaviors. According to the Diagnostic and Statistical Manual of Mental Disorders (APA, 2022 ), criteria to diagnose PTSD include the appearance of intrusive symptoms, avoidance of stimuli associated with trauma, alteration of mood and thinking significant alteration of arousal, and the possible presence of dissociative experiences.…”

Section: Ptsd and Emdrmentioning

confidence: 99%

“…According to the Diagnostic and Statistical Manual of Mental Disorders (APA, 2022 ), criteria to diagnose PTSD include the appearance of intrusive symptoms, avoidance of stimuli associated with trauma, alteration of mood and thinking significant alteration of arousal, and the possible presence of dissociative experiences. At the brain level, evidence shows that neural, neurochemical, and neurobiological alterations induce processing segregation within short-circuits, with structures belonging to the limbic, motor, and sensory systems, storing implicit traumatic memories, and becoming separated from hippocampal-cortical system processing episodic autobiographical memories (Vermetten and Lanius, 2012 ; Ressler et al, 2022 ).…”

Section: Ptsd and Emdrmentioning

confidence: 99%

Sensorimotor Interaction Against Trauma

et al. 2022

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Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model

Xiao,

Xi,

Wang

et al. 2023

Advanced Science

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Impaired extinction of fear memory is one of the most common symptoms in post‐traumatic stress disorder (PTSD), with limited therapeutic strategies due to the poor understanding of its underlying neural substrates. In this study, functional screening is performed and identified hyperactivity in the mediodorsal thalamic nucleus (MD) during fear extinction. Furthermore, the encoding patterns of the hyperactivated MD is investigated during persistent fear responses using multiple machine learning algorithms. The anterior cingulate cortex (ACC) is also identified as a functional downstream region of the MD that mediates the extinction of fear memory. The thalamocortical circuit is comprehensively analyzed and found that the MD‐ACC parvalbumin interneurons circuit is preferentially enhanced in PTSD mice, disrupting the local excitatory and inhibitory balance. It is found that decreased phosphorylation of the Kv3.2 channel contributed to the hyperactivated MD, primarily to the malfunctioning thalamocortical circuit. Using a lipid nanoparticle‐based RNA therapy strategy, channelopathy is corrected via a methoxylated siRNA targeting the protein phosphatase 6 catalytic subunit and restored fear memory extinction in PTSD mice. These findings highlight the function of the thalamocortical circuit in PTSD‐related impaired extinction of fear memory and provide therapeutic insights into Kv3.2‐targeted RNA therapy for PTSD.

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Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits

Cited by 210 publications

References 249 publications

Neural Oscillations in Aversively Motivated Behavior

Neural Oscillations in Aversively Motivated Behavior

Sensorimotor Interaction Against Trauma

Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model

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