Pyk2 suppresses contextual fear memory in a kinase-independent manner

Post-traumatic stress disorder (PTSD) is a psychological illness characterized by recalling a feeling of distress when re-experiencing the original trauma-related cues. This associative fear response plays an important role in some psychiatric disorders and elucidation of the underlying mechanisms is of great importance. Here, we constructed Pyk2 null mice and found that these mutant mice showed enhancement in contextual-fear memory, but no changes in auditory-cued and spatial-referenced learning and memory. Moreover, using kinase mutant mice, we observed that Pyk2 suppressed contextual fear memory in a kinase-independent pathway. Using high-throughput RNA sequencing, we found that immediate early genes (IEGs), such as Npas4 , c Fos , Zif268/Egr1 , Arc , and Nr4a1 , were enhanced in Pyk2 null mice. We further demonstrated that Pyk2 disruption affected pyramidal neuronal complexity and spine dynamics. Thus, we demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provides a model for understanding fear-related disorders.