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BACKGROUND AND AIMS: Fear extinction is a useful model for exposure-based therapies for the treatment of human anxiety disorders, such as phobias and posttraumatic stress disorder. Extinction of conditioned fear leads to formation of a new memory trace. Extinction memory is susceptible to the change of environment (context) in which conditioned stimulus (CS) is presented (promoting fear renewal), and to the passage of time (leading to spontaneous recovery of fear). Though the return of fear after extinction is a considerable challenge for the efficacy of exposure-based therapies, the neuronal basis of this phenomenon is not fully understood. METHODS: To understand better the neuronal bases of extinction memory, we characterize the amygdalar and hippocampal active projections to prefrontal cortex during retrieval of extinction memory. We use anterograde tracing in a transgenic rat in which neurons express a dendritically-targeted PSD-95:Venus fusion protein under the control of a c-fos promoter. Rats were subjected to auditory fear conditioning, followed by fear extinction and then presented to the extinguished CS in the extinction or fear conditioning context. RESULTS: Rats showed low levels of freezing when tested in the extinction context 24 hours after extinction and high levels of fear when tested in the conditioning context (either 24 hour or 28 days after extinction) or in the extinction context after 28 days (spontaneous recovery). The analysis of active projections shows that prefrontal cortex receives equal number of inputs from both basolateral amygdala and ventral hippocampus. However, the basolateral projections are dominant in neurons activated by high levels of fear. CONCLUSION: The obtained results suggest that basolateral inputs to the prefrontal cortex may drive retrieval of fear memory, as opposed to hippocampal inputs.
Extinction of conditioned fear leads to formation of a new memory trace. There are, however, factors altering behaviors associated with such a memory trace, such as CS presentation outside the extinction context (promoting fear renewal) and re-emerging of fear with the passage of time after extinction (spontaneous recovery). The neuronal basis of these phenomena is poorly understood. The involvement of hippocampal-prefrontal cortical circuits was investigated only during initial processing of fear extinction memory. As has been shown before for fear conditioning, the mechanisms underlying matured memory may differ from those of recent memory. In our study we used c-Fos immunohistochemistry to generate a functional map of the neural circuits involved in contextual retrieval of recent and remote memories of extinguished fear. Presentation of the CS in the extinction context 24 h after extinction yielded low freezing and induced strong activation of infralimbic cortex (IL) and ventral hippocampus (vHIPP). Similar presentation after 28 days resulted in high freezing and much lower activity of IL and vHIPP. In contrast, presentation of the CS outside the extinction context after either 24 h or 28 days yielded high freezing and induced strong activation of prelimbic cortex. These results suggest remodelling of the fear extinction memory trace over time, as well as dissociable neuronal mechanisms underlying fear renewal and spontaneous recovery.
INTRODUCTION: In fear extinction, a model of exposure-based therapy, a tone-conditioned stimulus previously paired with a footshock is presented repeatedly in the absence of the aversive outcome, resulting in fear reduction. It is well documented that the dorsal (including the prelimbic area, PL) and the ventral (the infralimbic area, IL) regions of the medial prefrontal cortex (mPFC) differentially regulate conditioned fear responses. The PL stimulation increases, whereas the IL stimulation decreases fear expression. In addition, the IL is critical for consolidation of extinction memories. Little is known, however, how different parts of the prefrontal cortex interact with each other and how their activity changes in the course of the extinction training. AIM(S): We aimed at detailed description of neural activity changes within the PL and IL during fear extinction. METHOD(S): We performed single unit recordings simultaneously in the PL and IL, during the habituation and two sessions of fear extinction in freely moving mice. Recorded neurons were divided into excitatory pyramidal cells and interneurons. The neuronal responses to the conditioned stimuli were analyzed and the activity of significantly responsive neurons was averaged. RESULTS: We found patterns of the single unit activity that differed along the dorso‑ventral axis of the mPFC. The averaged IL activity followed the behavior during the extinction session, while the PL pronouncedly showed inhibition during the fear expression at the beginning of the extinction session but not at later times. CONCLUSIONS: The results suggest different involvement of the PL and IL during the acquisition of extinction association, with the PL being mostly active during the high fear state, while the IL being active throughout the entire extinction session. The analysis of the mPFC activity suggests that its ventral region is mostly involved in the change of the association value from the perceiving conditioned stimuli as a threatful to the point of perceiving it as safe. FINANCIAL SUPPORT: ERC.
Posttraumatic stress disorder (PTSD) develops following exposure to a traumatic event, afflicting 7–12% of the population. Women are shown to be twice as likely as men to develop PTSD. Moreover, their susceptibility to PTSD following a trauma depending on the phase of menstrual cycle. Clarification of the biological mechanism underlying sex differences in the susceptibility to PTSD is necessary to design sexspecific therapies. We addressed this issue using an animal model of extinction and renewal of conditioned fear. We investigated the impact of estrus cycle phase on fear memory acquisition, extinction and recall. We hypothesized that hormonal status would influence memory formation and recall at all stages of the behavioral procedure. Therefore we employed a matrix design, carrying out fear conditioning, extinction and fear/extinction memory recall in either estrus or metaestrus. Males and gonadectomized have been trained at corresponding time intervals While estrus cycle phase during fear conditioning did not affect the retrieval of fear memory, hormonal status during both extinction and following fear/extinction memory recall affected animals’ freezing rates. Highest differences have been found in animals that have been tested in metaestrus and extinguished in estrus or metaestrus. Collectively, we claim that it is necessary to control the hormonal status of female animals used in experiments involving fear conditioning, extinction and renewal.
Występowanie koszatki Dryomys nitedula w Tatrzańskim Parku Narodowym jest słabo poznane. Od ponad 45 lat nie było informacji o obserwacji tego gatunku w tym rejonie. Dnia 29 lipca 2011 roku jeden osobnik koszatki został odłowiony w żywołowną pułapkę typu Sherman w obrębie ochronnym Zazadnia (Tatry Wschodnie). Koszatkę stwierdzono na wysokości 910 m n.p.m. w lesie świerkowo-jodłowym
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