Abstract

Social interactions are typically impaired in neuropsychiatric disorders such as autism, for which the genetic underpinnings are very complex. Social interactions can be modeled by analysis of behaviors, including social spacing, sociability, and aggression, in simpler organisms such as Drosophila melanogaster. Here, we examined the effects of mutants of the autism-related gene neuroligin 3 (nlg3) on fly social and non-social behaviors. Startled-induced negative geotaxis is affected by a loss of function nlg3 mutation. Social space and aggression are also altered in a sex- and social-experience-specific manner in nlg3 mutant flies. In light of the conserved roles that neuroligins play in social behavior, our results offer insight into the regulation of social behavior in other organisms, including humans.

Highlights

  • Social interactions amongst individuals within a group are important for the development of normal social behavior, which can have strong effects on survival and reproduction

  • We investigated the role of nlg3 in Drosophila social behavior using several assays to assess social interactions in groups of flies: social space [35] and sociability [11]

  • INteldg3eleexvpatreedssion in theNellagv3 >exnplrge3sslionne watatsw~i6cetitmheesahmioguhnetr othf atnhethceoncotrnotl,rodli(sSpulapypinlgemaelnetaakryy eFfifgeuctr.eHSo1w).ever, Nlg3 exSpirnecsesiothneirnetwheaeslanvo>enffleg3ctlionne swoacsia~l6stpimacees hinignhlegr3tLh0a4notrhnelcgo3nGtSr3o2l.rest of our analysisSionncentlhge3rDeewf1 ams nuotaenfftesc, tinonasdodciiatilosnpatcoeflinienslgo3vLe04roerxpnlrge3sGsSi3n2 mg untlagn3t.s, we focused the rest of our analysis on nlg3Def1 mutants, in addition to flies overexpressing nlg3

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Summary

Introduction

Social interactions amongst individuals within a group are important for the development of normal social behavior, which can have strong effects on survival and reproduction. We found that females Canton-S displayed lower levels of Nlg, and that coincides with differences reported in transcripts levels in Flybase Both nlg3L04 and nlg3GS32 flies were not different in social space. Male nlg3Def flies were more aggressive at an older age, and females had decreased dSO avoidance at both ages This was the first time the role of Drosophila nlg was examined in the context of social behavior. Nlg protein abundance did not change in control flies after isolation, nor at older ages (until 21 days—data not shown) This lack of change in Nlg protein contrasts with high-through studies reporting decreases in transcript levels, with social experience [34] and with age [53]. Using Drosophila’s powerful genetic tools to understand how nlg modulates social behavior and the response to the social environment will allow the identification of interacting genes and could lead to identifying new targets for pharmaceutical treatment of neuropsychiatric disorders such as autism

Materials and Methods
Isolation of cDNA Containing nlg3 ORF and UAS Transgene for Overexpression
Fly Stocks and Husbandry
Antibody Production
Western Blot and Protein Analysis
Fly Handling Prior to Behavior
Social Space Assay and ImageJ Analysis
Sociability
Aggression
4.11. Climbing
4.12. Activity
4.13. Social Isolation
Findings
4.14. Statistical Analysis
Full Text
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