Animals can remember a situation associated with an aversive event. contextual fear memory is initially encoded and consolidated in the hippocampus and gradually consolidated in multiple brain regions over time, including the medial prefrontal cortex (PFC). However, it is not fully understood how PFC neurons contribute to contextual fear memory formation during learning. In the present study, neuronal activity was increased in PFC neurons utilizing the pharmacogenetic hM3Dq-system in male mice. We show that fear expression and memory formation are enhanced by increasing neuronal activity in pfc during conditioning phase. Previous studies showed that the activation of hM3Dq receptor in a subset of amygdala neurons enhanced fear memory formation and biased which neurons are allocated to a memory trace, in which immediate early gene c-fos was preferentially expressed following memory retrieval in these pre-activated neurons. In this study, hM3Dq activation in PFC could not change the probability of c-fos expression in pre-activated neurons flowing memory retrieval. Instead, the number c-fos positive neurons following memory retrieval was significantly increased in the basolateral amygdala. our results suggest that neuronal activity in pfc at the time of learning modulates fear memory formation and downstream cellular activity at an early phase. Memories of fearful events can be retained for extended periods of time, which allows animals to predict danger; thus, this process is important for their survival. In humans, the formation of strong fear memory can drive the development of neuropsychiatric disorders, such as posttraumatic stress disorder (PTSD). Both the hippocampus and amygdala are critical structures for contextual fear memory formation 1,2. The contribution of the hippocampus to contextual fear memory retrieval decreases over time 1,3,4. Alternatively, some cortical areas such as the PFC and the anterior cingulate cortex gradually become more impactful on memory retrieval 5-8. It is reported that PFC activity is associated with inappropriate fear in PTSD patients 9. The dorsal and ventral subdivisions of PFC regulate the expression and extinction of fear in rodents, respectively 10. Inactivation of the dorsal PFC interferes with the expression of fear in cued and contextual fear conditioning (CFC) 11-15. In the PFC, expression of conditioned fear is temporally controlled by oscillation of functional assemblies 16 , and stimulation of the BLA to PFC projection increases cue-associated freezing behavior 17. In contrast, inactivation of PFC and stimulating PFC to BLA projection during conditioning has a small influence on memory consolidation at an early phase 11,18. Nonetheless, it has been shown that micro-stimulation of the PFC during tone representation increases conditioned fear expression under low foot shock conditions 19. However, the contribution of PFC to consolidation in CFC at an early phase of learning is not fully understood. Recent works show that a subset of PFC neurons is rapidly tagged duri...

Calcium-dependent activator protein for secretion 1 (CAPS1) is a key molecule in vesicular exocytosis, probably in the priming step. However, CAPS1’s role in synaptic plasticity and brain function is elusive. Herein, we showed that synaptic plasticity and learning behavior were impaired in forebrain and/or hippocampus-specific Caps1 conditional knockout (cKO) mice by means of molecular, physiological, and behavioral analyses. Neonatal Caps1 cKO mice showed a decrease in the number of docked vesicles in the hippocampal CA3 region, with no detectable changes in the distribution of other major exocytosis-related molecules. Additionally, long-term potentiation (LTP) was partially and severely impaired in the CA1 and CA3 regions, respectively. CA1 LTP was reinforced by repeated high-frequency stimuli, whereas CA3 LTP was completely abolished. Accordingly, hippocampus-associated learning was severely impaired in adeno-associated virus (AAV) infection-mediated postnatal Caps1 cKO mice. Collectively, our findings suggest that CAPS1 is a key protein involved in the cellular mechanisms underlying hippocampal synaptic release and plasticity, which is crucial for hippocampus-associated learning.