Brain serotonin deficiency leads to social communication deficits in mice

Beis, Daniel; Holzwarth, Katrin; Flinders, M.; Bäder, Michael; Wöhr, Markus; Alenina, Natalia

doi:10.1098/rsbl.2015.0057

Cited by 37 publications

(16 citation statements)

References 12 publications

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“…Abnormal aggression towards female mice has been linked to altered levels of brain serotonin, with mice deficient in brain tryptophan hydroxylase 2 exhibiting hyperaggressive behavior towards their female interaction partners [ 45 ]. The hyperaggression in NL3 R451C mice, previously identified towards male intruder mice, was mitigated following treatment with risperidone, an antagonist with high affinity for both serotonin and dopamine receptors [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism

et al. 2017

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male NL3R451C and WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior in NL3R451C mice. NL3R451C mice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones in NL3R451C mice. This study is the first to show altered mating behavior in the NL3R451C mouse and has provided new insights into the aggressive phenotype in this model.

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Section: Discussionmentioning

confidence: 99%

Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism

et al. 2017

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“…To induce USV and measure reciprocal social interaction behaviour in juvenile mice (P26 ± 2), same-sex/same-genotype animal pairs consisting of non-littermates were allowed to socially interact for 5 min after one mouse had been habituated to the test environment for 1 min 47,76 . To enhance social motivation, mice were isolated for 24 h prior to testing.…”

Section: Methodsmentioning

confidence: 99%

Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice

et al. 2019

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In humans, genetic variants of DLGAP1-4 have been linked with neuropsychiatric conditions, including autism spectrum disorder (ASD). While these findings implicate the encoded postsynaptic proteins, SAPAP1-4, in the etiology of neuropsychiatric conditions, underlying neurobiological mechanisms are unknown. To assess the contribution of SAPAP4 to these disorders, we characterized SAPAP4-deficient mice. Our study reveals that the loss of SAPAP4 triggers profound behavioural abnormalities, including cognitive deficits combined with impaired vocal communication and social interaction, phenotypes reminiscent of ASD in humans. These behavioural alterations of SAPAP4-deficient mice are associated with dramatic changes in synapse morphology, function and plasticity, indicating that SAPAP4 is critical for the development of functional neuronal networks and that mutations in the corresponding human gene, DLGAP4, may cause deficits in social and cognitive functioning relevant to ASD-like neurodevelopmental disorders.

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“…However, more recent studies using transgenic mouse models with specific genetic depletions of serotonin (e.g. tryptophan hydroxylase-2, knockout mice that lack the rate limiting enzyme in the synthesis of serotonin; or Lmx-1b knockout mice that are devoid of serotonergic neurons) have not confirmed a clear increase in sexual activity in the absence of this neurotransmitter (Angoa-Perez, et al, 2015;Beis, et al, 2015;Liu, et al, 2011;Zhang, et al, 2013).…”

Section: Sexual Behaviors In the Absence Of Central Serotoninmentioning

confidence: 99%

Neuroanatomical dichotomy of sexual behaviors in rodents

Angoa‐Pérez

Kuhn

2015

Behavioural Pharmacology

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Much of the social behavior in which rodents engage is related to reproduction, such as maintaining a breeding territory, seeking mates, mating, and caring for their young. Rodents belong to the internally fertilizing species that require sexual behavior for reproduction. The dyadic, heterosexual patterns of most mammalian species are sexually dimorphic, but they also share mutual components in both sexes: sexual attraction is reciprocal, sexual initiative is assumed, appetitive behavior is engaged in, and mating involves consummatory and postconsummatory phases in females as well as in males. Serotonin, a phylogenetically ancient molecule, is the most widely distributed neurotransmitter in the brain and its signaling pathways are essential for numerous functions including sexual behavior. Since the late 1960s, brain serotonergic neurotransmission has been considered to exert an inhibitory influence on the neural mechanisms mediating sexual behavior. This contention was based mainly on the observations that a decrease in central serotonergic activity facilitated the elicitation of sexual behavior, whereas an increase in central serotonergic activity attenuated it. However, the discovery of over 14 types of serotonin receptors has added numerous layers of complexity to the study of serotonin and sexual behavior. Evidence shows that, upon activation, certain receptor subtypes facilitate, whereas some others suppress, sexual behavior, as well as sexual arousal and motivation. Furthermore, the role of these receptors has been shown to be different in the male and female sexes. The use of serotonergic pharmacological interventions, mouse strains with genetic polymorphisms causing alterations in the levels of brain serotonin, and animal models with genetic manipulations of various serotonin effectors has helped delineate the fundamental role of this neurotransmitter in the regulation of sexual behavior. This review aims to examine the basics of the components of female and male sexual behavior and the participation of the serotonin system in the modulation of these behaviors, with emphasis on rodents.

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Brain serotonin deficiency leads to social communication deficits in mice

Cited by 37 publications

References 12 publications

Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism

Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism

Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice

Neuroanatomical dichotomy of sexual behaviors in rodents

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