Negative Memory Engrams in the Hippocampus Enhance the Susceptibility to Chronic Social Defeat Stress
| Autor: | Tak Pan Wong, Alice S. Wong, Amanda Larosa, Vanessa Wong, Marie-Eve Di Raddo, Tian Rui Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Hippocampus Mice Transgenic Engram Biology Hippocampal formation Optogenetics Social defeat Cellular mechanism Mice 03 medical and health sciences 0302 clinical medicine Memory Cell density Animals Social avoidance CA1 Region Hippocampal Research Articles Neurons Depression General Neuroscience Dentate gyrus Social relation Mice Inbred C57BL 030104 developmental biology Neuroscience Stress Psychological 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Neuroscience. 39:7576-7590 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1958-18.2019 |
| Popis: | The hippocampus has been highly implicated in depression symptoms. Recent findings suggest that the expression and susceptibility of depression symptoms are related to the enhanced functioning of the hippocampus. We reasoned that hippocampal engrams, which represent ensembles of neurons with increased activity after memory formation, could underlie some contributions of the hippocampus to depression symptoms. Using the chronic social defeat stress (CSDS) model, we examined social defeat-related hippocampal engrams in mice that are either susceptible or resilient to the stressor. TetTag mice were used to label social defeat-related hippocampal ensembles by LacZ. Engram cells correspond to ensembles that were reactivated by the same stressor.Compared to resilient and non-stressed control mice, we found that in both the dorsal and ventral hippocampal CA1 regions, susceptible mice exhibited a higher reactivation of social defeat-related LacZ-labeled cells (i.e. engram cells). The density of CA1 engram cells correlated with the level of social avoidance. Using DREADD to reactivate social defeat-related but not neutral contextual stimuli-related CA1 engram cells decreased social interaction. Increased engram cells in susceptible mice were region specific and could not be found in the dentate gyrus. Susceptible mice exhibited more negative stimuli-, but not neutral stimuli-, related CA1 engram cells than resilient mice in the dorsal hippocampus. Finally, chronic, but not a short and subthreshold, social defeat protocol was necessary to increase CA1 engram cell density. Together, our findings reveal that the susceptibility to CSDS is regulated by hippocampal CA1 engrams for negative memory. Hippocampal engrams for negative memory may underlie the vulnerability and expression of cognitive symptoms in depression.Significance statementWe provided evidence that negative memory hippocampal engrams contribute to the susceptibility to developing depression-related behavior after chronic social defeat stress. The activation of positive memory engrams have been shown to alleviate depression-related behaviors, while our findings reveal the pathological roles of negative memory engrams that could lead to those behaviors. Increased negative memory engrams could be a downstream effect of the reported high hippocampal activity in animal models and patients with depression. Unlike affective symptoms, we know much less about the cellular mechanisms of the cognitive symptoms of depression. Given the crucial roles of hippocampal engrams in memory formation, enhanced reactivation of negative memory engrams could be an important cellular mechanism that underlies the cognitive symptoms of depression. |
| Databáze: | OpenAIRE |
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