Negative Memory Engrams in the Hippocampus Enhance the Susceptibility to Chronic Social Defeat Stress

Zhang, Tian Rui; Larosa, Amanda; Raddo, Marie-Eve Di; Wong, Vanessa; Wong, Anson; Wong, Tak Pan

doi:10.1523/jneurosci.1958-18.2019

Cited by 50 publications

(31 citation statements)

References 70 publications

(85 reference statements)

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“…Given the role of the vHC in modulating affective states, this finding fits with the notion that affective disorders and AUD are comorbid conditions that share circuit plasticity mechanisms 16 , 17 . Indeed chronic stress increases vHC excitability in a manner similar to chronic alcohol exposure 14 , 18 , 19 .…”

Section: Introductionmentioning

confidence: 97%

Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity

Bach

Ewin

Baldassaro

et al. 2021

Sci Rep

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The hippocampus, particularly its ventral domain, can promote negative affective states (i.e. stress and anxiety) that play an integral role in the development and persistence of alcohol use disorder (AUD). The ventral hippocampus (vHC) receives strong excitatory input from the basolateral amygdala (BLA) and the BLA-vHC projection bidirectionally modulates anxiety-like behaviors. However, no studies have examined the effects of chronic alcohol on the BLA-vHC circuit. In the present study, we used ex vivo electrophysiology in conjunction with optogenetic approaches to examine the effects of chronic intermittent ethanol exposure (CIE), a well-established rodent model of AUD, on the BLA-vHC projection and putative intrinsic vHC synaptic plasticity. We discovered prominent BLA innervation in the subicular region of the vHC (vSub). CIE led to an overall increase in the excitatory/inhibitory balance, an increase in AMPA/NMDA ratios but no change in paired-pulse ratios, consistent with a postsynaptic increase in excitability in the BLA-vSub circuit. CIE treatment also led to an increase in intrinsic network excitability in the vSub. Overall, our findings suggest a hyperexcitable state in BLA-vSub specific inputs as well as intrinsic inputs to vSub pyramidal neurons which may contribute to the negative affective behaviors associated with CIE.

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Section: Introductionmentioning

confidence: 97%

Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity

Bach

Ewin

Baldassaro

et al. 2021

Sci Rep

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“…BISELLI Et aL. Zhang, Larosa, et al (2019) showed that also negative memory (social defeat related) engram cells in the CA1 region of the hippocampus play a role in vulnerability to stress-induced depressive-like behaviour. Mice susceptible to CSDS in SI testing exhibited a higher reactivation of these engram cells in an additional subsequent social defeat session.…”

mentioning

confidence: 99%

Optogenetic and chemogenetic insights into the neurocircuitry of depression‐like behaviour: A systematic review

Biselli

Lange

Sablottny

et al. 2019

Eur J of Neuroscience

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Major depressive disorder (MDD) and its treatment are challenges for global health. Optogenetics and chemogenetics are driving MDD research forward by unveiling causal relations between cell type-specific control of neurons and depressive-like behaviour in rodents. Using a systematic search process, in this review, a set of 43 original studies applying optogenetic or chemogenetic techniques in rodent models of depression was identified. Our aim was to provide an examination of all available studies elucidating central neuronal mechanisms leading to depressive-like behaviour in rodents and thereby unveiling the most promising routes for future research. A complex interacting network of relevant structures, in which central circuitries causally related to depressive-like behaviour are implicated, has been identified. As most relevant structures emerge: medial prefrontal cortex, anterior cingulate cortex, amygdala, nucleus accumbens, ventral tegmental area, hippocampus and raphe nuclei. Further evidence, though examined by only few studies, emerges for structures like the lateral habenula, or medial dorsal thalamus. Most of the identified brain areas have previously been associated with MDD neuropathology, but now evidence can be provided for causal pathological mechanisms within a complex cortico-limbic reward circuitry. However, the studies also show conflicting results concerning the 10 |

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“…In a clinical study in which MRI brain scans were used to detect the volume of hippocampal subregions in depressed patients and healthy control subjects, the left CA1 region emerged as a potential marker of depression 58 . Some studies have shown that the CA1 region is closely related to the pathogenesis of depression models 59 , 60 . Furthermore, in the CNS of adult mammals, neurogenesis mainly occurs in two regions, one of which is the DG.…”

Section: Discussionmentioning

confidence: 99%

The positive effects of running exercise on hippocampal astrocytes in a rat model of depression

Luo

Tang

et al. 2021

Transl Psychiatry

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Running exercise has been shown to alleviate depressive symptoms, but the mechanism of its antidepressant effect is still unclear. Astrocytes are the predominant cell type in the brain and perform key functions vital to central nervous system (CNS) physiology. Mounting evidence suggests that changes in astrocyte number in the hippocampus are closely associated with depression. However, the effects of running exercise on astrocytes in the hippocampus of depression have not been investigated. Here, adult male rats were subjected to chronic unpredictable stress (CUS) for 5 weeks followed by treadmill running for 6 weeks. The sucrose preference test (SPT) was used to assess anhedonia of rats. Then, immunohistochemistry and modern stereological methods were used to precisely quantify the total number of glial fibrillary acidic protein (GFAP)+ astrocytes in each hippocampal subregion, and immunofluorescence was used to quantify the density of bromodeoxyuridine (BrdU)+ and GFAP+ cells in each hippocampal subregion. We found that running exercise alleviated CUS-induced deficit in sucrose preference and hippocampal volume decline, and that CUS intervention significantly reduced the number of GFAP+ cells and the density of BrdU+/GFAP+ cells in the hippocampal CA1 region and dentate gyrus (DG), while 6 weeks of running exercise reversed these decreases. These results further confirmed that running exercise alleviates depressive symptoms and protects hippocampal astrocytes in depressed rats. These findings suggested that the positive effects of running exercise on astrocytes and the generation of new astrocytes in the hippocampus might be important structural bases for the antidepressant effects of running exercise.

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Negative Memory Engrams in the Hippocampus Enhance the Susceptibility to Chronic Social Defeat Stress

Cited by 50 publications

References 70 publications

Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity

Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity

Optogenetic and chemogenetic insights into the neurocircuitry of depression‐like behaviour: A systematic review

The positive effects of running exercise on hippocampal astrocytes in a rat model of depression

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