Single-neuron and Genetic Correlates of Autistic Behavior in Macaque

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2016 Sep 29

PMID 27679817

Citations 24

Authors

Kyoko Yoshida

Yasuhiro Go

Itaru Kushima

Atsushi Toyoda

Asao Fujiyama

Hiroo Imai

Nobuhito Saito

Atsushi Iriki

Norio Ozaki

Masaki Isoda

Affiliations

Soon will be listed here.

Abstract

Atypical neurodevelopment in autism spectrum disorder is a mystery, defying explanation despite increasing attention. We report on a Japanese macaque that spontaneously exhibited autistic traits, namely, impaired social ability as well as restricted and repetitive behaviors, along with our single-neuron and genomic analyses. Its social ability was measured in a turn-taking task, where two monkeys monitor each other's actions for adaptive behavioral planning. In its brain, the medial frontal neurons responding to others' actions, abundant in the controls, were almost nonexistent. In its genes, whole-exome sequencing and copy number variation analyses identified rare coding variants linked to human neuropsychiatric disorders in 5-hydroxytryptamine (serotonin) receptor 2C () and adenosine triphosphate (ATP)-binding cassette subfamily A13 (). This combination of systems neuroscience and cognitive genomics in macaques suggests a new, phenotype-to-genotype approach to studying mental disorders.

Citing Articles

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References

Brent L, Heilbronner S, Horvath J, Gonzalez-Martinez J, Ruiz-Lambides A, Robinson A . Genetic origins of social networks in rhesus macaques. Sci Rep. 2013; 3:1042. PMC: 3540398. DOI: 10.1038/srep01042. View

Xie E, Zhu L, Zhao L, Chang L . The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant. Genomics. 1996; 35(3):551-61. DOI: 10.1006/geno.1996.0397. View

Davis K, Stewart D, Friedman J, Buchsbaum M, Harvey P, Hof P . White matter changes in schizophrenia: evidence for myelin-related dysfunction. Arch Gen Psychiatry. 2003; 60(5):443-56. DOI: 10.1001/archpsyc.60.5.443. View

Oberman L, Hubbard E, McCleery J, Altschuler E, Ramachandran V, Pineda J . EEG evidence for mirror neuron dysfunction in autism spectrum disorders. Brain Res Cogn Brain Res. 2005; 24(2):190-8. DOI: 10.1016/j.cogbrainres.2005.01.014. View

Roth B, Hamblin M, Ciaranello R . Developmental regulation of 5-HT2 and 5-HT1c mRNA and receptor levels. Brain Res Dev Brain Res. 1991; 58(1):51-8. DOI: 10.1016/0165-3806(91)90236-c. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Gurevich I, Tamir H, Arango V, Dwork A, Mann J, Schmauss C . Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron. 2002; 34(3):349-56. DOI: 10.1016/s0896-6273(02)00660-8. View

Canton H, Emeson R, Barker E, Backstrom J, Lu J, Chang M . Identification, molecular cloning, and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing. Mol Pharmacol. 1996; 50(4):799-807. View

Yoshida K, Saito N, Iriki A, Isoda M . Representation of others' action by neurons in monkey medial frontal cortex. Curr Biol. 2011; 21(3):249-53. DOI: 10.1016/j.cub.2011.01.004. View

10.

Prades C, Arnould I, Annilo T, Shulenin S, Chen Z, Orosco L . The human ATP binding cassette gene ABCA13, located on chromosome 7p12.3, encodes a 5058 amino acid protein with an extracellular domain encoded in part by a 4.8-kb conserved exon. Cytogenet Genome Res. 2003; 98(2-3):160-8. DOI: 10.1159/000069852. View

11.

Segman R, Heresco-Levy U, Finkel B, Inbar R, Neeman T, Schlafman M . Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2Cser and DRD3gly alleles to susceptibility. Psychopharmacology (Berl). 2001; 152(4):408-13. DOI: 10.1007/s002130000521. View

12.

Luppino G, Calzavara R, Rozzi S, Matelli M . Projections from the superior temporal sulcus to the agranular frontal cortex in the macaque. Eur J Neurosci. 2001; 14(6):1035-40. DOI: 10.1046/j.0953-816x.2001.01734.x. View

13.

Dakin S, Frith U . Vagaries of visual perception in autism. Neuron. 2005; 48(3):497-507. DOI: 10.1016/j.neuron.2005.10.018. View

14.

Theoret H, Halligan E, Kobayashi M, Fregni F, Tager-Flusberg H, Pascual-Leone A . Impaired motor facilitation during action observation in individuals with autism spectrum disorder. Curr Biol. 2005; 15(3):R84-5. DOI: 10.1016/j.cub.2005.01.022. View

15.

Perrett D, Smith P, Mistlin A, Chitty A, Head A, POTTER D . Visual analysis of body movements by neurones in the temporal cortex of the macaque monkey: a preliminary report. Behav Brain Res. 1985; 16(2-3):153-70. DOI: 10.1016/0166-4328(85)90089-0. View

16.

Liu Z, Li X, Zhang J, Cai Y, Cheng T, Cheng C . Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2. Nature. 2016; 530(7588):98-102. DOI: 10.1038/nature16533. View

17.

Jellema T, Baker C, Wicker B, Perrett D . Neural representation for the perception of the intentionality of actions. Brain Cogn. 2000; 44(2):280-302. DOI: 10.1006/brcg.2000.1231. View

18.

Sikora D, Pettit-Kekel K, Penfield J, Merkens L, Steiner R . The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2006; 140(14):1511-8. DOI: 10.1002/ajmg.a.31294. View

19.

Zilbovicius M, Boddaert N, Belin P, Poline J, Remy P, Mangin J . Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography. Am J Psychiatry. 2000; 157(12):1988-93. DOI: 10.1176/appi.ajp.157.12.1988. View

20.

Trapnell C, Pachter L, Salzberg S . TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009; 25(9):1105-11. PMC: 2672628. DOI: 10.1093/bioinformatics/btp120. View