Prefrontal-amygdalar oscillations related to social interaction behavior in mice

The medial prefrontal cortex and amygdala are involved in the regulation of social behavior and associated with psychiatric diseases but their detailed neurophysiological mechanisms at a network level remain unclear. We recorded local field potentials (LFPs) from the dorsal medial PFC (dmPFC) and basolateral amygdala (BLA) while mice engaged on social behavior. We found that in wild-type mice, both the dmPFC and BLA increased 4–7 Hz oscillation power and decreased 30–60 Hz power when they needed to attend to another target mouse. In mouse models with reduced social interactions, dmPFC 4–7 Hz power further increased especially when they exhibited social avoidance behavior. In contrast, dmPFC and BLA decreased 4–7 Hz power when wild-type mice socially approached a target mouse. Frequency-specific optogenetic manipulations of replicating social approach-related LFP patterns restored social interaction behavior in socially deficient mice. These results demonstrate a neurophysiological substrate of the prefrontal cortex and amygdala related to social behavior and provide a unified pathophysiological understanding of neuronal population dynamics underlying social behavioral deficits.

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Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

eLife ◽

10.7554/elife.13442 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 118

Author(s):

Mar Gacias ◽

Sevasti Gaspari ◽

Patricia-Mae G Santos ◽

Sabrina Tamburini ◽

Monica Andrade ◽

...

Keyword(s):

Gene Expression ◽

Prefrontal Cortex ◽

Social Behavior ◽

Gut Microbiota ◽

Nod Mice ◽

Mouse Strains ◽

Social Avoidance ◽

Nonobese Diabetic ◽

Gene Environment ◽

Transcriptional Changes

Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior.

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Increased expression of schizophrenia-associated gene C4 leads to hypoconnectivity of prefrontal cortex and reduced social interaction

10.1101/598342 ◽

2019 ◽

Author(s):

Ashley L. Comer ◽

Tushare Jinadasa ◽

Lisa N. Kretsge ◽

Thanh P.H. Nguyen ◽

Jungjoon Lee ◽

...

Keyword(s):

Prefrontal Cortex ◽

Social Interaction ◽

Social Behavior ◽

Social Interactions ◽

Confocal Imaging ◽

Immune Gene ◽

Causative Role ◽

Severe Mental Disorder ◽

Brain Disorder ◽

Spine Development

ABSTRACTSchizophrenia is a severe mental disorder with an unclear pathophysiology. Increased expression of the immune gene C4 has been linked to a greater risk of developing schizophrenia; however, it is unknown whether C4 plays a causative role in this brain disorder. Using confocal imaging and whole-cell electrophysiology, we demonstrate that overexpression of C4 in mouse prefrontal cortex neurons leads to perturbations in dendritic spine development and hypoconnectivity, which mirror neuropathologies found in schizophrenia. We find evidence that microglia-neuron interactions and microglia-mediated synaptic engulfment are enhanced with increased expression of C4. We also show that C4-dependent circuit dysfunction in the frontal cortex leads to decreased social interactions in juvenile mice. These results demonstrate that increased expression of the schizophrenia-associated gene C4 causes aberrant circuit wiring in the developing prefrontal cortex and leads to deficits in early social behavior, suggesting that altered C4 expression contributes directly to schizophrenia pathogenesis.

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A new model as an early life manipulation: Fake mother

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.315 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S346-S346

Author(s):

M. Kucukkarapinar ◽

A. Dönmez ◽

S. Candansayar ◽

A. Bozkurt ◽

E. Akçay

Keyword(s):

Prefrontal Cortex ◽

Social Interaction ◽

Social Behavior ◽

Aggressive Behavior ◽

Early Life ◽

Social Interaction Test ◽

Protein Levels ◽

Maternal Odor ◽

Interaction Test

IntroductionEarly life stressful events cause long-term neural changes that are associated with psychiatric disorders.ObjectiveEarly life manipulations focus on commonly the impact of remaining separate from the mother in a specific period of time. The maternal odor is required for pups to approach the mother for nursing. What happens when there is a mother that smell like a real mother but does not take care her own pups?AimTo investigate the fake mother effects on adult rat's behavioral changes, NMDR2B protein level changes in prefrontal cortex and hippocampus.MethodsWistar rats were used. Fake mother (n:13), early handling (n:12), maternal separation (n:14) and control (n:12) were the study groups. A fake mother is an object that smells like a real dam. When the real mother is separated from own pups fake mother stays with the pups for an hour. Manipulations were made during the postnatal first 14 days. Behavioral tests (social interaction test, elevated plus maze, novel object recognition test) were made between postnatal 62 and 78 days. NMDAR2B protein levels in prefrontal cortex and hippocampus were evaluated by using ELISA at postnatal 78 days.ResultsIn social interaction test, fake mother group exhibited less social behavior and more aggressive behavior than the other groups. Their long-term memory functions were the lowest. NMDAR2B protein levels in the hippocampus increased in rats that exposed to early stressful life events.ConclusionThese results support that being raised by fake mother increases aggressive behavior and decrease social behavior in adulthood.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Sex-dependent effects of traumatic stress on social behavior and neuronal activation in the prefrontal cortex and amygdala

10.1101/2021.12.16.473017 ◽

2021 ◽

Author(s):

Mariia Dorofeikova ◽

Chandrashekhar D Borkar ◽

Katherine Weissmuller ◽

Lydia Smith-Osborne ◽

Samhita Basavanhalli ◽

...

Keyword(s):

Prefrontal Cortex ◽

Social Interaction ◽

Social Behavior ◽

Acute Stress ◽

Negative Impact ◽

Early Gene ◽

Central Nucleus ◽

Dependent Manner ◽

Neuronal Activation ◽

Footshock Stress

Social behavior is complex and fundamental, and deficits in social behavior are common pathological features for a variety of psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Acute stress has a negative impact on social behavior, and these effects may vary based on sex. The aim of this study was to explore the effect of footshock stress on the sociability of male and female C57Bl/6J mice. Animals were divided into two main groups of footshock exposure or context exposure control. Each group had mice that were treated with either the benzodiazepine alprazolam, or vehicle. Neuronal activation during social interaction was assessed using immunohistochemistry against the immediate early gene product cFos. Footshock stress induced a significantly increased latency to approach a social interaction counterpart in both sexes. Stress-induced increases in defensive tail-rattling behavior elicited during the sociability test were sex-dependent and alleviated by alprazolam. Alprazolam also lowered social exploration and neuronal activation in the infralimbic medial prefrontal cortex. Social interaction induced sex-dependent differences in cFos activation in the lateral subdivision of the central nucleus of the amygdala and ventromedial intercalated cell clusters. Overall, our results suggest that acute footshock stress induces alterations in sociability and patterns of cFos activation in a sex-dependent manner.

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Social Interactions of DAT-HET Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy

10.20944/preprints202105.0404.v1 ◽

2021 ◽

Author(s):

Anna Brancato ◽

Sara Lo Russo ◽

Anna Sara Liberati ◽

Cristiana Carbone ◽

Silvia Zelli ◽

...

Keyword(s):

Prefrontal Cortex ◽

Social Interaction ◽

Social Behavior ◽

Social Preference ◽

Male Rats ◽

Preclinical Model ◽

Genetic Trait ◽

Knock Out ◽

Noradrenaline Transporter ◽

Comparable Control

Social interaction is essential for life and is impaired in many psychiatric disorders like schizophrenia, au-tism, depression and major anxiety disorder. Monoamine transmission plays a key role in social behavior and both genetic and epigenetic modifications of dopamine and noradrenaline neurotransmission-related genes can affect the levels of social interaction. Since heterozygous individuals for a specific genetic trait possess only one mutant allele of that trait, in order to better evaluate the role of the interaction between genetics and epigenetics in unmasking latent genetically-determined predispositions, our interest has focused on studying the interplay between genetics and epigenetics influences on social behavior in male rats obtained by two different breeding schemes: a first group by breeding of knock-out (KO) male rats with wild-type (WT) female dams (homogeneous heterozygous offspring, termed MAT-HET), and a second group of heterozygous DAT male offspring by breeding of KO male and DAT-heterozygous female subjects (to obtain comparable control pups, termed MIX-HET). Their social behavior was then assessed by partner preference, social preference and elicited preference tests. In the first test MIX-HET and MAT-HET male mice had choice between two WT females one in estrous and the other not in estrous. In the second test they met either a MIX-HET or a WT male rodent. Also, the expression of the noradrenaline transporter (NET) was assessed in the prefrontal cortex, hippocampus and hypothalamus of MAT, MIX and WTs by immunofluorescence in order to estimate its involvement in the expression of social behavior. Our results show that MIX-HET focal rodents tend to have an asocial behavior when in contact with a female in estrous, and their behavior is similar to when the stimulus is a MIX-HET male. MAT-HET male rodents, instead, tend to be very attracted by the female in estrous, but they ignore the MIX-HET stimulus. MIX-HET progeny showed a lower expression of noradrenaline transporter in both hypothalamus and hippocampus with respect to MAT-HET rats, whereas MAT-HET rats displayed increased noradrenaline transporter immunofluorescence in the hypothalamus and in the hippocampus with respect to WT rats, while no difference was observed in the prefrontal cortex. Therefore we can hypothesize that the differences observed between the two heterozygous groups may be attributable to an epigenetic factor: the different maternal care received. These data can open new perspectives towards increased the preclinical knowledge about autism and bipolar disorder.

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The development of perineuronal nets around parvalbumin gabaergic neurons in the medial prefrontal cortex and basolateral amygdala of rats.

Behavioral Neuroscience ◽

10.1037/bne0000203 ◽

2017 ◽

Vol 131 (4) ◽

pp. 289-303 ◽

Cited By ~ 25

Author(s):

Kathryn D. Baker ◽

Arielle R. Gray ◽

Rick Richardson

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Basolateral Amygdala ◽

Gabaergic Neurons ◽

Perineuronal Nets

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Supporting Youth With Autism Learning Social Competence: A Comparison of Game- and Nongame-Based Activities in 3D Virtual World

Journal of Educational Computing Research ◽

10.1177/07356331211022003 ◽

2021 ◽

pp. 073563312110220

Author(s):

Xianhui Wang ◽

Wanli Xing

Keyword(s):

Social Interaction ◽

Social Competence ◽

Central Element ◽

Autism Spectrum ◽

Virtual Learning Environment ◽

Learning Activities ◽

Behavior Patterns ◽

Interaction Behavior ◽

Significant Difference ◽

The Impact

This study explored youth with Autism Spectrum Disorder (ASD) learning social competence in the context of innovative 3D virtual learning environment and the effects of gaming as a central element of the learning experience. The empirical study retrospectively compared the social interactions of 11 adolescents with ASD in game-and nongame-based 3D collaborative learning activities in the same social competence training curriculum. We employed a learning analytics approach - association rule mining to uncover the associative rules of verbal social interaction and nonverbal social interaction contributors from the large dataset of the coded social behaviors. By comparing the rules across the game and nongame activities, we found a significant difference in youth with ASD’s social performance. The results of the group comparison study indicated that the co-occurrence of verbal and nonverbal behaviors is much stronger in the game-based learning activities. The game activities also yielded more diverse social interaction behavior patterns. On the other hand, in the nongame activities, students’ social interaction behavior patterns are much more limited. Furthermore, the impact of game design principles on learning is then discussed in this paper.

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Ibotenic acid induced lesions impair the modulation of dendritic spine plasticity in the prefrontal cortex and amygdala, a phenomenon that underlies working memory and social behavior

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.173883 ◽

2021 ◽

Vol 896 ◽

pp. 173883

Author(s):

Néstor I. Martínez-Torres ◽

Nallely Vázquez-Hernández ◽

Fabiola L. Martín-Amaya-Barajas ◽

Mario Flores-Soto ◽

Ignacio González-Burgos

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Social Behavior ◽

Dendritic Spine ◽

Ibotenic Acid ◽

Spine Plasticity

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Imbalanced post- and extrasynaptic SHANK2A functions during development affect social behavior in SHANK2-mediated neuropsychiatric disorders

Molecular Psychiatry ◽

10.1038/s41380-021-01140-y ◽

2021 ◽

Author(s):

Ahmed Eltokhi ◽

Miguel A. Gonzalez-Lozano ◽

Lars-Lennart Oettl ◽

Andrey Rozov ◽

Claudia Pitzer ◽

...

Keyword(s):

Synaptic Plasticity ◽

Social Interaction ◽

Social Behavior ◽

Ampa Receptors ◽

Signal To Noise Ratio ◽

Signal Transmission ◽

Neuropsychiatric Disorders ◽

Autism Spectrum ◽

Strong Impact ◽

Odor Processing

AbstractMutations in SHANK genes play an undisputed role in neuropsychiatric disorders. Until now, research has focused on the postsynaptic function of SHANKs, and prominent postsynaptic alterations in glutamatergic signal transmission have been reported in Shank KO mouse models. Recent studies have also suggested a possible presynaptic function of SHANK proteins, but these remain poorly defined. In this study, we examined how SHANK2 can mediate electrophysiological, molecular, and behavioral effects by conditionally overexpressing either wild-type SHANK2A or the extrasynaptic SHANK2A(R462X) variant. SHANK2A overexpression affected pre- and postsynaptic targets and revealed a reversible, development-dependent autism spectrum disorder-like behavior. SHANK2A also mediated redistribution of Ca2+-permeable AMPA receptors between apical and basal hippocampal CA1 dendrites, leading to impaired synaptic plasticity in the basal dendrites. Moreover, SHANK2A overexpression reduced social interaction and increased the excitatory noise in the olfactory cortex during odor processing. In contrast, overexpression of the extrasynaptic SHANK2A(R462X) variant did not impair hippocampal synaptic plasticity, but still altered the expression of presynaptic/axonal signaling proteins. We also observed an attention-deficit/hyperactivity-like behavior and improved social interaction along with enhanced signal-to-noise ratio in cortical odor processing. Our results suggest that the disruption of pre- and postsynaptic SHANK2 functions caused by SHANK2 mutations has a strong impact on social behavior. These findings indicate that pre- and postsynaptic SHANK2 actions cooperate for normal neuronal function, and that an imbalance between these functions may lead to different neuropsychiatric disorders.

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