The Regulatory Effects Of Anteromedial Thalamic Nucleus Corticotropin-Releasing Factor Neurons On Cued Fear Expression

Fear is a basic physiological mechanism of animals.It prompts animals to make correct defense and response in time under dangerous conditions,so as to maximize the survival probability of individuals.Under the condition of acute stress,the hypothalamic-pituitary-adrenal(HPA)axis will be activated,and the autonomic nervous system will be combined to regulate the emotional and behavioral responses of animals.Corticotropin-releasing factor(CRF)is the main driving force of HPA axis and plays an important role in coordinating neuroendocrine stress response.Studies have shown that CRF is widely distributed in the marginal and cortical areas of the central nervous system,besides in the hypothalamus.CRF is not only a neuroendocrine hormone,but also a neuroregulatory factor widely involved in regulating the neurological activity and the emotional and cognitive functions of animals.The ventral portion of the anteromedial thalamic nucleus(AMv)is in a position to convey information to cortico-hippocampal-amygdalar circuits involved in the processing of fear memory.However,it remains to be determined whether the nucleus is involved in the acquisition or expression of conditioned fear.In this study,morphological staining,chemical genetics and behavioral testing were used to specifically study the possible regulatory effects of CRF neurons in AMv on conditioned fcar behavior in animals.In this study,CRF-Cre transgenic mice were used as experimental subjects.It was found that CRF neurons had distribution in the bilateral AMv regions of mice.Using fear conditioning model,we found that cued fear expression increased c-Fos protein expression in AMv CRF neurons.Then we used chemical genetic methods to specifically manipulate AMv CRF neurons to explore their role in cued fear conditioning of animals.It was found that specific activation of AMv CRF neurons during the fear expression could increase the freezing rates of mice during auditory-cued fear expression,and maintain a high level of fear.Specific inhibition of AMv CRF neurons during fear expression can reduce the freezing rate of mice during auditory-cued fear expression,and accelerate the decline of fear level.At the same time,specific activation or inhibition of AMv CRF neurons during fear training did not change the fear response of mice during training or fear expression.After changing the auditory cue to odor cue,the same increase in fear level still occurred in the activation group,but not in the inhibition group.These results suggest that AMv CRF neurons can regulate the fear expression of cued fear in mice,but not the acquisition of fear.AMv projections were also examined,and it was found that AMv CRF neurons had projections to the prefrontal cortex(including medial prefrontal cortex and orbital cortex),ectorhinal area,entorhinal area,perirhinal area,subiculum,CA1,retrosplenial cortex and the basolateral part of amygdala,of which the projections to the prefrontal cortex were the most intensive.After specific activation of AMV CRF neurons by chemical genetics,we observed obvious c-Fos signals in the medial prefrontal cortex,ectorhinal area,entorhinal area and perirhinal area,suggesting that AMv CRF neurons have significant excitatory projections to these areas,and this projection may be involved in the regulation of conditioned fear behavior.