scholarly journals Ventral hippocampus interacts with prelimbic cortex during inhibition of threat response via learned safety in both mice and humans

2019 ◽  
Vol 116 (52) ◽  
pp. 26970-26979 ◽  
Author(s):  
Heidi C. Meyer ◽  
Paola Odriozola ◽  
Emily M. Cohodes ◽  
Jeffrey D. Mandell ◽  
Anfei Li ◽  
...  

Heightened fear and inefficient safety learning are key features of fear and anxiety disorders. Evidence-based interventions for anxiety disorders, such as cognitive behavioral therapy, primarily rely on mechanisms of fear extinction. However, up to 50% of clinically anxious individuals do not respond to current evidence-based treatment, suggesting a critical need for new interventions based on alternative neurobiological pathways. Using parallel human and rodent conditioned inhibition paradigms alongside brain imaging methodologies, we investigated neural activity patterns in the ventral hippocampus in response to stimuli predictive of threat or safety and compound cues to test inhibition via safety in the presence of threat. Distinct hippocampal responses to threat, safety, and compound cues suggest that the ventral hippocampus is involved in conditioned inhibition in both mice and humans. Moreover, unique response patterns within target-differentiated subpopulations of ventral hippocampal neurons identify a circuit by which fear may be inhibited via safety. Specifically, ventral hippocampal neurons projecting to the prelimbic cortex, but not to the infralimbic cortex or basolateral amygdala, were more active to safety and compound cues than threat cues, and activity correlated with freezing behavior in rodents. A corresponding distinction was observed in humans: hippocampal–dorsal anterior cingulate cortex functional connectivity—but not hippocampal–anterior ventromedial prefrontal cortex or hippocampal–basolateral amygdala connectivity—differentiated between threat, safety, and compound conditions. These findings highlight the potential to enhance treatment for anxiety disorders by targeting an alternative neural mechanism through safety signal learning.

2019 ◽  
Author(s):  
Samantha Ortiz ◽  
Maeson S. Latsko ◽  
Julia L. Fouty ◽  
Sohini Dutta ◽  
Jordan M. Adkins ◽  
...  

AbstractNearly one third of Americans have been afflicted with an anxiety disorder. A common symptom of anxiety disorders is the over generalization of fear across a broad range of contextual cues. We previously found that the anterior cingulate cortex and ventral hippocampus (vHPC) regulate generalized fear. Here, we investigate the functional projections from the ACC and vHPC to the amygdala and their role in governing generalized fear in a preclinical rodent model. A chemogenetic approach (DREADDs) was used to inhibit glutamatergic projections from the ACC or vHPC that terminate within the basolateral amygdala (BLA) at recent (1 day) or remote (28 days) time points after contextually fear conditioning male mice. Inactivating ACC or vHPC projections to the BLA significantly reduced generalized fear to a novel, nonthreatening context but had no effect on fear to the training context. Further, our data indicate that the ACC-BLA circuit supports generalization in a time-independent manner. We also identified for the first time a strictly time-dependent role of the vHPC-BLA circuit in supporting remote generalized contextual fear. Dysfunctional signaling to the amygdala from the ACC or the hippocampus could underlie over-generalized fear responses that are associated with anxiety disorders. Our findings demonstrate that the ACC and vHPC regulate fear expressed in novel, nonthreatening environments via projections to the BLA but do so as a result of training intensity or time, respectively.Significance StatementAnxiety disorders are characterized by a common symptom that promotes overgeneralization of fear in non-threatening environments. Dysregulation of the amygdala, anterior cingulate cortex (ACC), or hippocampus has been hypothesized to contribute to increased fear associated with anxiety disorders. Our findings show that the ACC and HPC projections to the basolateral amygdala regulate generalized fear in non-threatening, environments. However, descending ACC projections control fear generalization independent of time, whereas HPC projections play a strictly time-dependent role in regulating generalized fear. Thus, dysfunctional ACC/HPC signaling to the BLA may be a predominant underlying mechanism of non-specific fear associated with anxiety disorders. Our data have important implications for predictions made by theories about aging memories and interactions between the hippocampus and cortical regions.


2007 ◽  
Author(s):  
Stacy R. Freiheit ◽  
Christine Esser ◽  
Christopher Vye ◽  
Rebecca Swan

2020 ◽  
Vol 17 (3) ◽  
pp. 318-324 ◽  
Author(s):  
Khadije Saket ◽  
Jalil T. Afshari ◽  
Ehsan Saburi ◽  
Mahdi Yousefi ◽  
Roshanak Salari

From ancient times, medicinal plants have been usually utilized to treat many disorders, but today, interest in these herbs is again aroused, because of their fewer side effects and low-cost. In traditional medicine, for many diseases, various medicinal herbs have been suggested so far. Drimia maritime, also named squill, is an important medicinal plant for the treatment of many diseases, especially respiratory diseases. In the current evidence-based study, we conducted a review of the general characteristics, ingredients, administration form, and side effects of squill in traditional medicine. For this purpose, traditional Persian medicine literatures and electronic databases were examined including PubMed, Scopus, and Google Scholar. Many compounds are isolated from D.maritima, including scillaren, scillirubroside, scillarenin, and bufadienolide glycosides. Oxymel is the most commonly used form of squill for various diseases, especially respiratory diseases. Besides, squill has been used in the treatment of cardiovascular, digestive, and dermatological disorders, it is also used against various cancer cells for its antioxidant and cytotoxic properties. Moreover, there is relatively reliable evidence of its benefits for bacterial and helminthic infections, rheumatism, edema, gout, abortion induction, healing of wounds and urine induction. It seems that supplementary studies are required to explore the bioactive agents and their effective mechanisms.


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