Regulation of Social Memory by Lateral Entorhinal Cortical Projection to Dorsal Hippocampal CA2

Dang, Rui; Zhou, Yu; Zhang, Yue; Liu, Die; Wu, Miao; Liu, An; Jia, Zhengping; Xie, Wei

doi:10.1007/s12264-021-00813-6

Cited by 20 publications

(14 citation statements)

References 16 publications

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“…The goal of this study was to investigate mitochondrial heterogeneity in the mouse hippocampus. Focusing on the enrichment of MCU in area CA2, we unexpectedly uncovered that MCU expression is preferentially enriched in CA2 distal apical dendrites, precisely where CA2 neurons receive layer-specific input from entorhinal cortex II, a circuit recently shown to carry social information to CA2 (Dang et al, 2022;Lopez-Rojas et al, 2022). This striking enrichment of MCU in CA2 distal dendrites compared to CA2 proximal dendrites and neighboring CA1 dendrites is not seen with another mitochondrial marker, COX4, suggesting that mitochondria in CA2 distal dendrites have a unique molecular expression profile.…”

Section: Discussionmentioning

confidence: 95%

Layer‐specific mitochondrial diversity across hippocampal CA2 dendrites

et al. 2023

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CA2 is an understudied subregion of the hippocampus that is critical for social memory. Previous studies identified multiple components of the mitochondrial calcium uniporter (MCU) complex as selectively enriched in CA2. The MCU complex regulates calcium entry into mitochondria, which in turn regulates mitochondrial transport and localization to active synapses. We found that MCU is strikingly enriched in CA2 distal apical dendrites, precisely where CA2 neurons receive entorhinal cortical input carrying social information. Furthermore, MCU-enriched mitochondria in CA2 distal dendrites are larger compared to mitochondria in CA2 proximal apical dendrites and neighboring CA1 apical dendrites, which was confirmed in CA2 with genetically labeled mitochondria and electron microscopy. MCU overexpression in neighboring CA1 led to a preferential localization of MCU in the proximal dendrites of CA1 compared to the distal dendrites, an effect not seen in CA2. Our findings demonstrate that mitochondria are molecularly and structurally diverse across hippocampal cell types and circuits, and suggest that MCU can be differentially localized within dendrites, possibly to meet local energy demands.

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Section: Discussionmentioning

confidence: 95%

Layer‐specific mitochondrial diversity across hippocampal CA2 dendrites

et al. 2023

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“…The goal of this study was to investigate mitochondrial heterogeneity in the mouse hippocampus. Focusing on the enrichment of MCU in area CA2, we unexpectedly uncovered that MCU expression is preferentially enriched in CA2 distal apical dendrites, precisely where CA2 neurons receive layer-specific input from entorhinal cortex II, a circuit recently shown to carry social information to CA2 (Lopez-Rojas et al 2022; Dang et al 2022). This striking enrichment of MCU in CA2 distal dendrites compared to CA2 proximal dendrites and neighboring CA1 dendrites is not seen with another mitochondrial marker, COX4, suggesting that mitochondria in CA2 distal dendrites have a unique molecular expression profile.…”

Section: Discussionmentioning

confidence: 94%

Layer-specific mitochondrial diversity across hippocampal CA2 dendrites

Pannoni

Gil

Campbell

et al. 2021

Preprint

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CA2 is an understudied subregion of the hippocampus that is critical for social memory. Previous studies identified multiple components of the mitochondrial calcium uniporter (MCU) complex as selectively enriched in CA2, however the functional significance of this enrichment remains unclear. The MCU complex regulates calcium entry into mitochondria, which in turn regulates mitochondrial transport and localization to active synapses. We found that MCU is strikingly enriched in CA2 distal apical dendrites, precisely where CA2 neurons receive entorhinal cortical input carrying social information. Further, MCU-enriched mitochondria in CA2 distal dendrites are larger compared to mitochondria in CA2 proximal apical dendrites and neighboring CA1 apical dendrites. Genetic knockdown of MCU in CA2 resulted in smaller mitochondria in CA2 distal dendrites, indicating that MCU expression plays a role in regulating mitochondrial mass in CA2. MCU overexpression in neighboring CA1 led to larger mitochondria preferentially in proximal dendrites compared to distal dendrites and GFP controls. Our findings demonstrate that mitochondria are molecularly and structurally diverse across hippocampal cell types and circuits, and that MCU expression cell-autonomously regulates mitochondrial mass, but layer-specific dendritic localization depends on cell type. Our data support the idea that CA2 mitochondria are functionally distinct from CA1 mitochondria, which may confer unique synaptic and circuit properties underlying CA2 function in social memory.

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“…The c-Fos protein expression is enhanced during memory retrieval (Smith et al, 2016, Xing et al, 2021Dang et al, 2022). Juvenile stress attenuated neuronal activity within the hippocampal CA2 in adulthood, which correlates with the social memory impairment.…”

Section: Adult Ca2 C-fos Expression Diminish By Juvenile Stressmentioning

confidence: 95%

“…The CA3 is also a distinct region responsible for encoding spatial memory and pattern separation (Cherubini and Miles, 2015). Due to its susceptibility to both neurodegeneration and seizures (Song et al, 2018;Yu et al, 2016), many take interest in its dysfunction and how it contributes to memory deficits (Brun et al, 2002;Holden and Gilbert, 2012;Liu et al, 2022;Roozendaal et al, 2001;Sandi et al, 2003). Thus, studying subregions of the hippocampus is important to distinguish between their unique functions and subsequent impairments that explain behavioural and cognitive abnormalities.…”

Section: Overview Of the Hippocampusmentioning

confidence: 99%

“…When adults were finished with acquisition of the social memory test, they were returned to their home cages that contained their cagemate. During those 30 minutes, there may have been activation of the CA2 (Dang et al, 2022;Lim, 2020;Oliva et al, 2020) which in turn may cause to question whether the expression of c-Fos was due to subject's interaction with their cagemate.…”

Section: Limitationsmentioning

confidence: 99%

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Juvenile Stress: A Sensitive Period of Vulnerability on Hippocampal CA2 and Social Recognition Memory

Maletta¹

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Social memory involves social recognition: the ability to discriminate between two or more conspecifics. Animals must distinguish between conspecifics so they can engage in behaviour that leads to ideal outcomes. Recently, it was discovered that the CA2 region of the hippocampus is essential for social memory, as lesions and dysfunction to the area lead to social memory impairments. Early life stress (ELS) has been found to cause social memory impairments as well as the conditions where these impairments occur such as schizophrenia and autism spectrum disorder. In this study, we examined whether impairments in social memory observed after juvenile stress were due to malfunction within the CA2. Long-Evans rats were exposed to stress using a social stressor between P19-21. Using the social discrimination test, social memory was defined as increased interactions towards a novel juvenile rat in contrast to a previously-encountered juvenile from 30 minutes prior. Tissue was then collected to determine c-Fos expression within the CA2 using nickel-enhanced 3,3'-Diaminobenzidine (DAB) immunohistochemistry. We demonstrated that adults exposed to juvenile stress did not differ from controls in sociability. However, unlike controls, they were unable to discriminate between a novel and previously encountered conspecific showing social recognition deficits, with a greater decrease in performance for females. In addition, we determined that juvenile stress was associated with significantly decreased c-Fos-positive cells within the CA2, exhibiting reduced neuronal activity within the region. These findings indicate that the CA2 is vulnerable to stress during the juvenile period, with long-term effects that persist throughout adulthood.

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Regulation of Social Memory by Lateral Entorhinal Cortical Projection to Dorsal Hippocampal CA2

Cited by 20 publications

References 16 publications

Layer‐specific mitochondrial diversity across hippocampal CA2 dendrites

Layer‐specific mitochondrial diversity across hippocampal CA2 dendrites

Layer-specific mitochondrial diversity across hippocampal CA2 dendrites

Juvenile Stress: A Sensitive Period of Vulnerability on Hippocampal CA2 and Social Recognition Memory

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