Biology subjects

Cincotta, C.

Publications and source records attributed to Cincotta, C..

3 recordsLinked to original sources

bioRxiv2020

Chronic activation of fear engrams induces extinction-like behavior in ethanol-exposed mice

Alcohol withdrawal directly impacts the brains stress and memory systems, which may underlie individual susceptibility to persistent drug and alcohol-seeking behaviors. Numerous studies demonstrate that forced alcohol abstinence, which may lead to withdrawal, can impair fear-related memory processes in rodents such as extinction learning, however the underlying neural circuits mediating these impairments remain elusive. Here, we tested an optogenetic strategy aimed at mitigating fear extinction impairments in male c57BL/6 mice following exposure to alcohol (i.e., ethanol) and forced abstinence. In the first experiment, extensive behavioral extinction training in a fear-conditioned context was impaired in ethanol-exposed mice compared to controls. In the second experiment, neuronal ensembles processing a contextual fear memory in the dorsal hippocampus were tagged and optogenetically reactivated repeatedly in a distinct context in ethanol-exposed and control mice. Chronic activation of these cells resulted in a context-specific, extinction-like reduction in fear responses in both control and ethanol-exposed mice. These findings suggest that while ethanol can impair fear extinction learning, optogenetic manipulation of a fear engram is sufficient to induce an extinction-like reduction in fear responses.

neuroscience↗

bioRxiv2020

Chronic optogenetic stimulation of hippocampal engrams variably modulates social behaviors in mice

The hippocampus processes both spatial-temporal information and emotionally salient experiences. To test the functional properties of discrete sets of cells in the dorsal dentate gyrus (dDG), we examined whether chronic optogenetic reactivation of these ensembles was sufficient to modulate social behaviors in mice. We found that chronic reactivation of dDG cells in male mice was sufficient to enhance social behaviors in a female exposure task when compared to pre-stimulation levels. However, chronic reactivation of these cells was not sufficient to modulate group differences in a separate subset of social behaviors, and multi-region analysis of neural activity did not yield detectable differences in immediate-early gene expression or neurogenesis, suggesting a dissociation between our chronic stimulation-induced behavioral effects and underlying neural responses. Together, our results demonstrate that chronic optogenetic stimulation of cells processing valent experiences enduringly and unidirectionally modulates social interactions between male and female mice.

neuroscience↗

bioRxiv2019

Hippocampus and amygdala fear memory engrams re-emerge after contextual fear reinstatement

The formation and extinction of fear memories represent two forms of learning that each engage the hippocampus and amygdala. How cell populations in these areas contribute to fear relapse, however, remains unclear. Here, we demonstrate that, in male mice, cells active during fear conditioning in the dentate gyrus of hippocampus exhibit decreased activity during extinction and are re-engaged after contextual fear relapse. In vivo calcium imaging reveals that relapse drives population dynamics in the basolateral amygdala to revert to a network state similar to the state present during fear conditioning. Finally, we find that optogenetic inactivation of neuronal ensembles active during fear conditioning in either the hippocampus or amygdala is sufficient to disrupt fear expression after relapse. These results suggest that fear relapse triggers a partial re-emergence of the original fear memory representation, providing new insight into the neural substrates of fear relapse.

neuroscience↗