Atypical perineuronal nets in the CA2 region interfere with social memory in a mouse model of social dysfunction

2021 ◽  
Author(s):  
Elise C. Cope ◽  
Anna D. Zych ◽  
Nicole J. Katchur ◽  
Renée C. Waters ◽  
Blake J. Laham ◽  
...  
Keyword(s):  
Mouse Model ◽  
Social Memory ◽  
Perineuronal Nets ◽  
Social Dysfunction

scholarly journals Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a mouse model of schizophrenia

2019 ◽  
Author(s):  
Macayla L. Donegan ◽  
Fabio Stefanini ◽  
Torcato Meira ◽  
Joshua A. Gordon ◽  
Stefano Fusi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Social Interactions ◽  
Pyramidal Neurons ◽  
Social Memory ◽  
Spatial Location ◽  
Memory Deficits ◽  
Spatial Coding ◽  
Social Stimuli ◽  
The Social ◽  
22Q11.2 Microdeletion

AbstractThe hippocampal CA2 region is essential for social memory and has been implicated in neuropsychiatric disorders. However, little is known about how CA2 neural activity encodes social interactions and how this coding is altered in disease. We recorded from CA2 pyramidal neurons as mice engaged in social interactions and found that while CA2 failed to stably represent spatial location, CA2 activity encoded contextual changes and novel social stimuli. In the Df(16)A+/- mouse model of the human 22q11.2 microdeletion, a major schizophrenia risk factor, CA2 activity showed a surprising increase in spatial coding while failing to encode social novelty, consistent with the social memory deficit in these mice. Previous work has shown that CA2 pyramidal neurons are hyperpolarized in Df(16)A+/- mice, likely as a result of upregulation of TREK-1 K+ current. We found that administration of a TREK-1 antagonist rescued the social memory deficits and restored normal CA2 coding properties in Df(16)A+/- mice, supporting a crucial role for CA2 in the encoding of novel social stimuli and social dysfunction.

scholarly journals EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer’s disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Lindsay Poppe ◽  
Laura Rué ◽  
Mieke Timmers ◽  
Annette Lenaerts ◽  
Annet Storm ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dendritic Spine ◽  
Cognitive Functions ◽  
Social Memory ◽  
Beta Amyloid ◽  
Amyloid Peptide ◽  
Spine Morphology ◽  
Model Of Alzheimer’S Disease

Abstract Background EphA4 is a receptor of the ephrin system regulating spine morphology and plasticity in the brain. These processes are pivotal in the pathophysiology of Alzheimer’s disease (AD), characterized by synapse dysfunction and loss, and the progressive loss of memory and other cognitive functions. Reduced EphA4 signaling has been shown to rescue beta-amyloid-induced dendritic spine loss and long-term potentiation (LTP) deficits in cultured hippocampal slices and primary hippocampal cultures. In this study, we investigated whether EphA4 ablation might preserve synapse function and ameliorate cognitive performance in the APPPS1 transgenic mouse model of AD. Methods A postnatal genetic ablation of EphA4 in the forebrain was established in the APPPS1 mouse model of AD, followed by a battery of cognitive tests at 9 months of age to investigate cognitive function upon EphA4 loss. A Golgi-Cox staining was used to explore alterations in dendritic spine density and morphology in the CA1 region of the hippocampus. Results Upon EphA4 loss in APPPS1 mice, we observed improved social memory in the preference for social novelty test without affecting other cognitive functions. Dendritic spine analysis revealed altered synapse morphology as characterized by increased dendritic spine length and head width. These modifications were independent of hippocampal plaque load and beta-amyloid peptide levels since these were similar in mice with normal versus reduced levels of EphA4. Conclusion Loss of EphA4 improved social memory in a mouse model of Alzheimer’s disease in association with alterations in spine morphology.

scholarly journals Neonatal oxytocin impacts hippocampal network development and restores adult social memory in a mouse model of autism

2020 ◽  
Author(s):  
Alessandra Bertoni ◽  
Fabienne Schaller ◽  
Roman Tyzio ◽  
Stephane Gaillard ◽  
Francesca Santini ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurodevelopmental Disorders ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Social Memory ◽  
Strong Impact ◽  
Adult Mice ◽  
Ca3 Neurons ◽  
The Brain ◽  
Deficient Mice

AbstractPrader-Willi (PW) and Schaaf-Yang (SY) syndromes are genetic neurodevelopmental disorders involving MAGEL2 gene. Magel2-deficient mice mimic the symptoms common to both diseases, in particular autistic-like symptoms. Importantly, peripheral administration of oxytocin during infancy cures social deficiency of Magel2-KO mice beyond treatment into adulthood. However, neurobiological alterations related to oxytocin-signaling and responsible for social deficits are poorly explored in mouse models of autism, including Magel2-deficient mice. Moreover, the mechanisms by which neonatal oxytocin-administration improves social behavior remain unknown. Here, by studying Magel2-KO mice, we aim to decipher the mechanisms underlying the PWS/SYS social alterations and their rescue by oxytocin.Hippocampal neurons in Dentate Gyrus and CA2/CA3 regions are associated with social memory engrams involving the oxytocin-system. We have shown that Magel2 and oxytocin-receptor are specifically co-expressed in those neurons during development. Then, in Magel2-deficient adult mice, we showed a deficit of social memory and revealed an increase of spontaneous inhibitory activity of pyramidal neurons, a higher number of somatostatin-positive interneurons and an increase in the number of oxytocin-receptors. We also showed a delay in the GABAergic developmental sequence in CA3 neurons associated with biochemical changes in potassium-chloride cotransporter KCC2. Importantly, we demonstrated a strong impact of neonatal oxytocin administration, rescuing all these neuronal alterations.This study elucidates the mechanisms by which peripheral oxytocin-administration in neonates affects the brain social circuitry. While clinical trials are ongoing, we are demonstrating the therapeutic value of administrating oxytocin in newborns to treat patients with Prader-Willi and Schaaf-Yang syndromes and possibly other neurodevelopmental disorders related to autism.Single sentence summaryThis study reveals how peripheral administration of oxytocin in newborns treats alterations in the brain social circuits described in a mouse model of autism.

scholarly journals Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome

Neuron ◽  
2016 ◽  
Vol 89 (1) ◽  
pp. 163-176 ◽  
Author(s):  
Rebecca A. Piskorowski ◽  
Kaoutsar Nasrallah ◽  
Anastasia Diamantopoulou ◽  
Jun Mukai ◽  
Sami I. Hassan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Social Memory ◽  
22Q11.2 Deletion Syndrome ◽  
Memory Deficit ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Age Dependent

scholarly journals Perineuronal Nets in the Prefrontal Cortex of a Schizophrenia Mouse Model: Assessment of Neuroanatomical, Electrophysiological and Behavioral Contributions

2021 ◽  
Vol 22 (20) ◽  
pp. 11140
Author(s):  
Razia Sultana ◽  
Charles Brady Brooks ◽  
Amita Shrestha ◽  
Olalekan Michael Ogundele ◽  
Charles Chulsoo Lee
Keyword(s):  
Prefrontal Cortex ◽  
Mouse Model ◽  
Neural Activity ◽  
Medial Temporal Lobe ◽  
Neurodevelopmental Disorder ◽  
Tail Suspension Test ◽  
Enzymatic Digestion ◽  
Behavioral Pattern ◽  
Perineuronal Nets ◽  
Model Assessment

Schizophrenia is a neurodevelopmental disorder whose etiopathogenesis includes changes in cellular as well as extracellular structures. Perineuronal nets (PNNs) associated with parvalbumin-positive interneurons (PVs) in the prefrontal cortex (PFC) are dysregulated in schizophrenia. However, the postnatal development of these structures along with their associated neurons in the PFC is unexplored, as is their effects on behavior and neural activity. Therefore, in this study, we employed a DISC1 (Disruption in Schizophrenia) mutation mouse model of schizophrenia to assess these developmental changes and tested whether enzymatic digestion of PNNs in the PFC affected schizophrenia-like behaviors and neural activity. Developmentally, we found that the normal formation of PNNs, PVs, and colocalization of these two in the PFC, peaked around PND 22 (postnatal day 22). However, in DISC1, mutation animals from PND 0 to PND 60, both PNNs and PVs were significantly reduced. After enzymatic digestion of PNNs with chondroitinase in adult animals, the behavioral pattern of control animals mimicked that of DISC1 mutation animals, exhibiting reduced sociability, novelty and increased ultrasonic vocalizations, while there was very little change in other behaviors, such as working memory (Y-maze task involving medial temporal lobe) or depression-like behavior (tail-suspension test involving processing via the hypothalamic pituitary adrenal (HPA) axis). Moreover, following chondroitinase treatment, electrophysiological recordings from the PFC exhibited a reduced proportion of spontaneous, high-frequency firing neurons, and an increased proportion of irregularly firing neurons, with increased spike count and reduced inter-spike intervals in control animals. These results support the proposition that the aberrant development of PNNs and PVs affects normal neural operations in the PFC and contributes to the emergence of some of the behavioral phenotypes observed in the DISC1 mutation model of schizophrenia.

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