Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole, significantly impairs extinction recall in male ...

While exposure therapy is effective in treating anxiety, fear can return after exposure. Return of fear can be understood through mechanisms of extinction learning. One form of return of fear is reinstatement, or, the fear that results from an unsignaled unconditional stimulus (US) presentation after extinction. Though the conditional response (CR; e.g., fear) typically reduces during extinctio...

Brain-derived neurotrophic factor (BDNF), the most abundant neutrophin in the mammalian central nervous system, is critically involved in synaptic plasticity. In both rodents and humans, BDNF has been implicated in hippocampus- and amygdala-dependent learning and memory and has more recently been linked to fear extinction processes. Fifty-nine healthy participants, genotyped for the functional ...

Previous studies have demonstrated that rats subjected to single prolonged stress (SPS) exhibit posttraumatic stress disorder (PTSD)-like symptoms, such as enhanced contextual fear in response to trauma-related and trauma-unrelated events. Furthermore, we previously reported that upregulation of hippocampal glycine transporter 1 (GlyT-1) mRNA after context exposure could be the initial mechanis...

The context in which fear memories are extinguished has important implications for treating human fear and anxiety disorders. Extinction of Pavlovian fear conditioning is context specific; after extinction, fear responses are reduced only in the extinction context and remain elevated in every other context. Contextual modulation of spike firing in the amygdala is a putative mechanism for the co...

Freezing has become the predominant measure used in rodent studies of conditioned fear, but conditioned suppression of reward-seeking behavior may provide a measure that is more relevant to human anxiety disorders; that is, a measure of how fear interferes with the enjoyment of pleasurable activities. Previous work has found that an isolated presentation of a fear conditioned stimulus (CS) prio...

BACKGROUND Current neurocircuitry models of anxiety disorders posit a lack of inhibitory tone in the amygdala during acquisition of Pavlovian fear responses and deficient encoding of extinction responses in amygdala-medial prefrontal cortex circuits. Competition between these two responses often results in a return of fear, limiting control over anxiety. However, one hypothesis holds that a pha...

Neuronal voltage gated calcium channels (VGCCs) are well known for its importance in synaptic transmission and signaling pathway in the specific circuits. On the other hand, the role of different VGCCs in the cognitive functions has not been studied. Although it has been reported that fear extinction requires Cav2.1-regulated N-methyl-D-aspartate (NMDA) receptor signaling, Cav2.2-regulated syna...

Recent findings reveal qualitative developmental differences in extinction of learned fear. The present study explored potential developmental differences in the role of NMDA in acquisition and extinction. Rats were injected with MK-801 prior to fear conditioning or extinction training. Acquisition was found to be NMDA dependent in both age groups, whereas extinction was found to be NMDA depend...

A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos-based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that ...