Pharmacological stimulation of infralimbic cortex after fear conditioning facilitates subsequent fear extinction.

The infralimbic (IL) division of the medial prefrontal cortex (mPFC) is a crucial site for the extinction of conditioned fear memories in rodents. Recent work suggests that neuronal plasticity in the IL that occurs during (or soon after) fear conditioning enables subsequent IL-dependent extinction learning. We therefore hypothesized that pharmacological activation of the IL after fear conditioning would promote the extinction of conditioned fear.

Acute stress yields a sex-dependent facilitation of signaled active avoidance in rats.

Post-traumatic stress disorder (PTSD) is a debilitating disorder characterized by excessive fear, hypervigilance, and avoidance of thoughts, situations or reminders of the trauma. Among these symptoms, relatively little is known about the etiology of pathological avoidance. Here we sought to determine whether acute stress influences avoidant behavior in adult male and female rats.

Ventral hippocampus mediates inter-trial responding in signaled active avoidance.

The hippocampus has a central role in regulating contextual processes in memory. We have shown that pharmacological inactivation of ventral hippocampus (VH) attenuates the context-dependence of signaled active avoidance (SAA) in rats. Here, we explore whether the VH mediates intertrial responses (ITRs), which are putative unreinforced avoidance responses that occur between trials.

Acute stress yields a sex-dependent facilitation of signaled active avoidance in rats.

Post-traumatic stress disorder (PTSD) is a debilitating disorder characterized by excessive fear, hypervigilance, and avoidance of thoughts, situations or reminders of the trauma. Among these symptoms, relatively little is known about the etiology of pathological avoidance. Here we sought to determine whether acute stress influences avoidant behavior in adult male and female rats.

Ventral hippocampus mediates inter-trial responding in signaled active avoidance.

The hippocampus has a central role in regulating contextual processes in memory. We have shown that pharmacological inactivation of ventral hippocampus (VH) attenuates the context-dependence of signaled active avoidance (SAA) in rats. Here, we explore whether the VH mediates intertrial responses (ITRs), which are putative unreinforced avoidance responses that occur between trials.

Neural circuits for the adaptive regulation of fear and extinction memory.

The regulation of fear memories is critical for adaptive behaviors and dysregulation of these processes is implicated in trauma- and stress-related disorders. Treatments for these disorders include pharmacological interventions as well as exposure-based therapies, which rely upon extinction learning. Considerable attention has been directed toward elucidating the neural mechanisms underlying fear and extinction learning.

Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear.

Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear.

Parvalbumin-Positive Interneurons in the Medial Prefrontal Cortex Regulate Stress-Induced Fear Extinction Impairments in Male and Female Rats.

Stress has profound effects on fear extinction, a form of learning that is essential to behavioral therapies for trauma-related and stressor-related disorders. Recent work reveals that acute footshock stress reduces medial prefrontal cortex (mPFC) activity that is critical for extinction learning. Reductions in mPFC activity may be mediated by parvalbumin (PV)-containing interneurons via feedforward inhibition imposed by amygdala afferents.

Basal forebrain cholinergic signaling in the basolateral amygdala promotes strength and durability of fear memories.

The basolateral amygdala (BLA) complex receives dense cholinergic projections from the nucleus basalis of Meynert (NBM) and the horizontal limb of the diagonal band of Broca (HDB). The present experiments examined whether these projections regulate the formation, extinction, and renewal of fear memories. This was achieved by employing a Pavlovian fear conditioning protocol and optogenetics in transgenic rats.

Nucleus reuniens inactivation does not impair consolidation or reconsolidation of fear extinction.

Recent data reveal that the thalamic nucleus reuniens (RE) has a critical role in the extinction of conditioned fear. Muscimol (MUS) infusions into the RE impair within-session extinction of conditioned freezing and result in poor long-term extinction memories in rats. Although this suggests that RE inactivation impairs extinction learning, it is also possible that it is involved in the consolidation of extinction memories.

Neural Oscillations in Aversively Motivated Behavior.

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.

Clinical trials in desmoid-type fibromatosis in children and adults: A systematic review.

Desmoid-type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm, which occurs in children and adults, with a peak incidence in young adults. For the majority of the patients, DTF is a chronic and symptomatic disease, which affects health-related quality of life. Systemic treatment regimens tend to differ for patients treated by pediatric oncologists compared to medical oncologists.

Sex differences in the immediate extinction deficit and renewal of extinguished fear in rats.

Extinction learning is central to exposure-based behavioral therapies for reducing fear and anxiety in humans. However, patients with fear and anxiety disorders are often resistant to extinction. Moreover, trauma and stress-related disorders are highly prone to relapse and are twice as likely to occur in females compared to males, suggesting that females may be more susceptible to extinction deficits and fear relapse phenomena.

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

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.

Estrous cycle contributes to state-dependent contextual fear in female rats.

The increased susceptibility of women to stress and trauma-related disorders compared to men suggests a role for ovarian hormones in modulating fear and anxiety. In both humans and rodents, estrogen and progesterone have been shown to influence fear learning during acquisition, expression, and extinction. Recently, we showed that allopregnanolone (ALLO), a progesterone (PROG) metabolite and GABA receptor potentiator, confers state-dependent contextual fear when infused into the bed nucleus of the stria terminalis of male rats.

Convergent Coding of Recent and Remote Fear Memory in the Basolateral Amygdala.

Background: In both rodents and humans, the basolateral amygdala (BLA) is essential for encoding and retrieving conditioned fear memories. Although the BLA is a putative storage site for these memories, recent evidence suggests that they become independent of the BLA with the passage of time.

Methods: We systematically examined the role for the BLA in the retrieval of recent (1 day) and remote (2 weeks) fear memory using optogenetic, electrophysiological, and calcium imaging methods in male and female Long-Evans rats.

Ventral hippocampus mediates the context-dependence of two-way signaled avoidance in male rats.

Considerable work indicates that instrumental responding is context-dependent, but the neural mechanisms underlying this phenomenon are poorly understood. Given the important role for the hippocampal formation in contextual processing, we hypothesized that reversible inactivation of the hippocampus would impair the context-dependence of active avoidance. To test this hypothesis, we used a two-way signaled active avoidance (SAA) task that requires rats to shuttle across a divided chamber during a tone CS in order to avoid a footshock US.

Behavioral and brain mechanisms mediating conditioned flight behavior in rats.

Environmental contexts can inform animals of potential threats, though it is currently unknown how context biases the selection of defensive behavior. Here we investigated context-dependent flight responses with a Pavlovian serial-compound stimulus (SCS) paradigm that evokes freeze-to-flight transitions. Similar to previous work in mice, we show that male and female rats display context-dependent flight-like behavior in the SCS paradigm.

Covert capture and attenuation of a hippocampus-dependent fear memory.

Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption.

Slow wave activity moderates the association between new learning and traumatic brain injury severity.

Study Objectives: Sleep-wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate to severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep-wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate to severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity.