Pharmacological modulation of Kv3 voltage-gated potassium channels regulates fear discrimination and expression in a response-dependent manner.

Various psychiatric diseases are characterized by aberrant cognition and emotional regulation. This includes inappropriately attributing affective salience to innocuous cues, which can be investigated using translationally relevant preclinical models of fear discrimination. Activity in the underpinning corticolimbic circuitry is governed by parvalbumin-expressing GABAergic interneurons, which also regulate fear discrimination.

Sex differences in auditory fear discrimination are associated with altered medial prefrontal cortex function.

The increased prevalence of post-traumatic stress disorder (PTSD) that is observed in women may involve sex differences in learned fear inhibition and medial prefrontal cortex (mPFC) function. PTSD is characterized by fear overgeneralization involving impaired fear regulation by safety signals. We recently found that males show fear discrimination and females show fear generalization involving reduced safety signalling after extended fear discrimination training.

The neurobiological basis of sex differences in learned fear and its inhibition.

Learning that certain cues or environments predict threat enhances survival by promoting appropriate fear and the resulting defensive responses. Adapting to changing stimulus contingencies by learning that such cues no longer predict threat, or distinguishing between these threat-related and other innocuous stimuli, also enhances survival by limiting fear responding in an appropriate manner to conserve resources. Importantly, a failure to inhibit fear in response to harmless stimuli is a feature of certain anxiety and trauma-related disorders, which are also associated with dysfunction of the neural circuitry underlying learned fear and its inhibition.

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders.

Anxiety and trauma-related disorders are psychiatric diseases with a lifetime prevalence of up to 25%. Phobias and post-traumatic stress disorder (PTSD) are characterized by abnormal and persistent memories of fear-related contexts and cues. The effects of psychological treatments such as exposure therapy are often only temporary and medications can be ineffective and have adverse side effects.

Sex differences in discriminating between cues predicting threat and safety.

Post-traumatic stress disorder (PTSD) is more prevalent in women than men. PTSD is characterized by overgeneralization of fear to innocuous stimuli and involves impaired inhibition of learned fear by cues that predict safety. While evidence indicates that learned fear inhibition through extinction differs in males and females, less is known about sex differences in fear discrimination and safety learning.