Activation of Entorhinal Cortical Projections to the Dentate Gyrus Underlies Social Memory Retrieval

Leung, Celeste; Cao, Fan; Nguyen, Robin; Joshi, Krutika; Aqrabawi, Afif J; Xia, Shuting; Cortez, Miguel A.; Snead, O. Carter; Kim, Jun Chul; Jia, Zhengping

doi:10.1016/j.celrep.2018.04.073

Cited by 69 publications

(53 citation statements)

References 50 publications

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“…There are some reports showing that adult-born neurons are important for spatial memory acquisition and retrieval (Gu et al, 2012;Tronel et al, 2015), yet less is known about adult-born neurons and memory maintenance/consolidation. While the dentate gyrus itself has been shown to be important for social memory retrieval (Leung et al, 2018), the link between this brain region and social memory maintenance has not been explored.…”

Section: Discussionmentioning

confidence: 99%

Adult-Born Neurons in the Hippocampus Are Essential for Social Memory Maintenance

Cope

Waters

Diethorn

et al. 2020

eNeuro

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Throughout adulthood, the dentate gyrus continues to produce new granule cells, which integrate into the hippocampal circuitry. New neurons have been linked to several known functions of the hippocampus, including learning and memory, anxiety and stress regulation, and social behavior. We explored whether transgenic reduction of adult-born neurons in mice would impair social memory and the formation of social dominance hierarchies. We utilized a conditional transgenic mouse strain (TK mice) that selectively reduces adult neurogenesis by treatment with the antiviral drug valganciclovir (VGCV). TK mice treated with VGCV were unable to recognize conspecifics as familiar 24 hr after initial exposure. We then explored whether reducing new neurons completely impaired their ability to acquire or retrieve a social memory and found that TK mice treated with VGCV were able to perform at control levels when the time between exposure (acquisition) and re-exposure (retrieval) was brief. We then explored whether adult-born neurons are involved in dominance hierarchy formation by analyzing their home cage behavior as well as their performance in the tube test, a social hierarchy test, and did not find any consistent alterations in behavior between control and TK mice treated with VGCV. These data suggest that adult neurogenesis is essential for social memory maintenance, but not for acquisition nor retrieval over a short time frame, with no effect on social dominance hierarchy. Future work is needed to explore whether the influence of new neurons on social memory is mediated through connections with the CA2, an area involved in social recognition. 3 Significance Statement Adult hippocampal neurogenesis has been implicated in behaviors linked to the hippocampus, including social behavior. We utilized a conditional transgenic mouse line to reduce adult-born neurons and explored social memory and social dominance hierarchy formation. We found that mice with reduced numbers of new neurons were unable to recognize conspecifics as familiar with a long delay after initial exposure but were able to recognize them as familiar with a short delay. We did not observe changes in social dominance as measured by home cage behavior or tube test performance in mice with reduced numbers of new neurons. These data confirm and extend previous reports to show that adult-born neurons are essential for maintenance but not for acquisition or short-term retrieval of social memories, nor for social dominance.

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Section: Discussionmentioning

confidence: 99%

Adult-Born Neurons in the Hippocampus Are Essential for Social Memory Maintenance

Cope

Waters

Diethorn

et al. 2020

eNeuro

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“…Cortical information largely enters the hippocampus via the perforant pathway from the entorhinal cortex which forms synapses onto the DG, CA3 and CA2 regions . Optogenetic inhibition of entorhinal inputs in the dorsal DG does not impact sociability but impairs social recognition in mice, implicating the EC‐DG synapse as an important component for social memory. However, another recent study shows that the deletion of the n ‐methyl‐ d ‐aspartate receptor (NMDAR) NR1 subunit from the DG granule cells—effectively eliminating NMDAR‐dependent plasticity—does not produce deficits in social memory of male mice .…”

Section: Oxytocin and Vasopressin Modulation Of Hippocampal‐dependentmentioning

confidence: 99%

“…58 Chemogenetic silencing of dorsal CA2 inputs to the ventral CA1 via local infusions of clozapine-n-oxide robustly impairs social memory, 99 further supporting a dorsal CA2 to ventral CA1 circuit underlying social memory. The CA1 also receives monosynaptic input from the EC, however, optical inhibition of this pathway in the ventral CA1 region does not impair social recognition, 92 suggesting information transfer from the CA2/CA3 region is more important for this task. Additionally, stimulation or inhibition of inputs from the basolateral amygdala to the ventral CA1 region of male mice bidirectionally influences social behavior.…”

Section: The Hippocampus and Social Memorymentioning

confidence: 99%

Oxytocin and vasopressin in the rodent hippocampus

Cilz

Cymerblit‐Sabba

Young

2018

Genes Brain and Behavior

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The role of the hippocampus in social memory and behavior is under intense investigation. Oxytocin (Oxt) and vasopressin (Avp) are two neuropeptides with many central actions related to social cognition. Oxt‐ and Avp‐expressing fibers are abundant in the hippocampus and receptors for both peptides are seen throughout the different subfields, suggesting that Oxt and Avp modulate hippocampal‐dependent processes. In this review, we first focus on the anatomical sources of Oxt and Avp input to the hippocampus and consider the distribution of their corresponding receptors in different hippocampal subfields and neuronal populations. We next discuss the behavioral outcomes related to social memory seen with perturbation of hippocampal Oxt and Avp signaling. Finally, we review Oxt and Avp modulatory mechanisms in the hippocampus that may underlie the behavioral roles for both peptides.

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“…The lack of discrimination between social targets in the social novelty test may indicate impairment in social memory 47 . It has been shown that hippocampal neurons mediate social memory 48 , and that neurons projecting from the cortex to the hippocampus can affect social memory without affecting sociability 49 . Understanding the differences in these models requires further study.…”

Section: Discussionmentioning

confidence: 99%

In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice

Bagnall-Moreau

Huerta

Comoletti

et al. 2020

Sci Rep

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the concept that exposure in utero to maternal anti-brain antibodies contributes to the development of autism spectrum disorders (ASD) has been entertained for over a decade. We determined that antibodies targeting Caspr2 are present at high frequency in mothers with brain-reactive serology and a child with ASD, and further demonstrated that exposure in utero to a monoclonal anti-Caspr2 antibody, derived from a mother of an ASD child, led to an-ASD like phenotype in male offspring. Now we propose a new model to study the effects of in utero exposure to anti-Caspr2 antibody. Dams immunized with the extracellular portion of Caspr2 express anti-Caspr2 antibodies throughout gestation to better mimic the human condition. Male but not female mice born to dams harboring polyclonal anti-Caspr2 antibodies showed abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as repetitive behaviors and impairments in novelty interest in the social preference test as adults. These data supporting the pathogenicity of anti-Caspr2 antibodies are consistent with the concept that anti-brain antibodies present in women during gestation can alter fetal brain development, and confirm that males are peculiarly susceptible. Autism spectrum disorder (ASD) affects 1 in every 58 children in the United States, and is 4 times more prevalent in boys than girls 1. ASD is diagnosed based on the presence of stereotypic behaviors and impairments in social skills and communication. Recent research has emphasized the importance of the in utero environment as a contributing risk factor for ASD. An elegant study demonstrated that siblings born within inter-birth interval of 18 months or less after the birth of a child with ASD have a higher risk for ASD than siblings born after an interval of 4 years or longer time period 2. Moreover, maternal half siblings of a child with ASD are more at risk for ASD than paternal half siblings 2. Several studies looking into maternal risk factors for having a child with ASD have highlighted the importance of infection 3-5 , microbiome 6-8 , and brain-reactive antibodies 9,10. For instance, women with autoimmune diseases such as rheumatoid arthritis (RA), celiac disease or systemic lupus erythematous (SLE) have an increased risk for a child with ASD 11,12. This association holds if the mother (but not the father) exhibits the autoimmune disease.

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Activation of Entorhinal Cortical Projections to the Dentate Gyrus Underlies Social Memory Retrieval

Cited by 69 publications

References 50 publications

Adult-Born Neurons in the Hippocampus Are Essential for Social Memory Maintenance

Adult-Born Neurons in the Hippocampus Are Essential for Social Memory Maintenance

Oxytocin and vasopressin in the rodent hippocampus

In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice

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