Browsing by Subject "Fear conditioning"
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Item Adult hippocampal neurogenesis modulates fear learning through associative and nonassociative mechanisms(2015-05) Seo, Dong-oh; Drew, Michael R., Ph. D.; Domjan, Michael P.; Jones, Theresa A.; Zemelman, Boris; Colgin, Laura L.Adult hippocampal neurogenesis is believed to support hippocampus-dependent learning and emotional regulation. These putative functions of adult neurogenesis have typically been studied in isolation, and little is known about how they interact to produce adaptive behavior. We used trace fear conditioning as a model system to elucidate mechanisms through which adult hippocampal neurogenesis modulates processing of aversive experience. To achieve a specific ablation of neurogenesis, we generated transgenic mice expressing herpes simplex virus thymidine kinase (HSV-TK) under the dcx gene promoter, which directs expression to neural progenitors and immature neurons. Intracerebralventricular injection of the prodrug ganciclovir (GCV) caused a robust suppression of neurogenesis without suppressing gliogenesis. Neurogenesis ablation via this method (DCX-TK/GCV system) or targeted x-irradiation caused an increase in context conditioning in trace but not delay fear conditioning. The data suggest that this phenotype represents opposing effects of neurogenesis ablation on associative and nonassociative components of fear learning. Arrest of neurogenesis sensitizes mice to nonassociative effects of fear conditioning, as evidenced by increased anxiety-like behavior in the open field after (but not in the absence of) fear conditioning. In addition, arrest of neurogenesis impairs associative trace conditioning, but this impairment can be masked by nonassociative fear. The results suggest that adult neurogenesis modulates emotional learning via two distinct but opposing mechanisms: it supports associative trace conditioning while also buffering against the generalized fear and anxiety caused by fear conditioning.Item Ventral hippocampal regulation of contextual fear and extinction memory(2023-12) Brockway, Emma Taylor; Drew, Michael R.; Colgin, Laura L; Dunsmoor, Joseph E; Zemelman, Boris V; Maren, StephenFear learning creates long-term memories through which predictive cues or the context surrounding the fearful event acquire negative associations. Later exposure to these stimuli elicits a fearful response, but this learned response will diminish in the absence of threat, a process known as extinction. Extinction does not abolish fear memory, but instead creates a separate memory of safety. The hippocampus is thought to be a hub for competition of the expression of these two opposing memories. Neural ensemble representations of contextual fear and extinction memories are distinct in the hippocampus, but how these memories are processed to influence recall and behavior is not known. These experiments sought to investigate activity in the ventral CA1 and subiculum (vHP), where projections to other fear and extinction related structures are located, to better understand how the hippocampus influences the expression and suppression of fear behavior. First, we investigated whether activity among vHP projections to the BLA and IL differed during context fear and extinction recall. We found that fear recall causes more activation of projections to BLA compared to IL, while extinction recall results in the opposite pattern of more activation of projections to IL than BLA. This shows that the ventral hippocampus is sensitive to the valence of contextual memory, and signals to relevant brain regions based on that valence. Next, we sought to selectively inhibit the projections from vHP to BLA and IL to test if these projections are indeed necessary for further recall of these memories. These manipulations were unsuccessful in impairing recall. Finally, we stimulated SST interneurons in vHP or IL to induce feed-forward inhibition. We found that stimulating vHP SST interneurons impaired fear recall, reducing fear behavior, and impaired extinction learning, resulting in higher fear behavior in a later test. This result demonstrates the vHP’s role in both context fear expression and suppression. Increasing inhibition in the IL did not affect context fear or extinction recall but did impair auditory cue extinction. Overall, these results provide evidence that vHP activity modulates context memory in a valence dependent way through connections to other fear related regions.