The Role of Fkbp5 in Anxiety Like Behaviors



 DESCRIPTION (provided by applicant): Dysfunction of the hypothalamic-pituitary-adrenal axis can lead to insufficient or excessive glucocorticoid secretion which can disrupt emotional learning by affecting brain structures such as the amygdala and the infralimbic cortex. Impaired glucocorticoid signaling affects fear extinction learning. In the proposed project, I will examine the glucocorticoid receptor interaction with one of its regulators, the FK binding protein 5 (Fkbp5). Since Fkbp5 polymorphisms are associated with increased risk of developing post-traumatic stress disorder, changes in Fkbp5 expression may affect fear extinction learning and recall. In Aim 1, I will examine the mRNA and protein changes in Fkbp5 in the infralimbic cortex, and blood during fear conditioning and fear extinction. In Aim 2, I will test whether reducing the expression of Fkbp5 by infusing a plasmid expressing an Fkbp5-shRNA into the infralimbic cortex prior fear extinction affects fear extinction recall. Also, in Aim 3, I will test whether changes in Fkbp5 expression in the infralimbic cortex contributes to the impaired extinction found after chronic glucocorticoid activation. The proposed experiments will shed light on the association between Fkbp5 and PTSD.