Anterior Cingulate Cortex and Ventral Hippocampal Inputs to the Basolateral Amygdala Selectively Control Generalized Fear
| Autor: | Julia L. Fouty, Aaron M. Jasnow, Jordan M. Adkins, Sohini Dutta, Maeson S. Latsko, Samantha Ortiz |
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| Rok vydání: | 2019 |
| Předmět: |
Hippocampus
Context (language use) Hippocampal formation Gyrus Cinguli Amygdala Generalization Psychological Mice 03 medical and health sciences 0302 clinical medicine Neural Pathways medicine Animals Fear conditioning Research Articles Anterior cingulate cortex 030304 developmental biology 0303 health sciences Basolateral Nuclear Complex General Neuroscience Fear medicine.disease Rats Mice Inbred C57BL medicine.anatomical_structure nervous system Anxiety medicine.symptom Psychology Neuroscience Anxiety disorder 030217 neurology & neurosurgery Basolateral amygdala |
| Zdroj: | The Journal of Neuroscience. 39:6526-6539 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Nearly 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. |
| Databáze: | OpenAIRE |
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