Research ArticlePSYCHOLOGY

Single-neuron and genetic correlates of autistic behavior in macaque

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Science Advances  21 Sep 2016:
Vol. 2, no. 9, e1600558
DOI: 10.1126/sciadv.1600558
  • Fig. 1 Behavioral task.

    (A) Temporal sequence of events in the role-reversal task. An example of a single trial in which monkey N was the actor and monkey E was the observer is shown. After the actor had pressed a start button (illuminated in red) for 1000 to 1500 ms, two target buttons turned on in two different colors (green and yellow), the positions of which were randomized across trials. In the example shown, the actor chose the green button. Both monkeys were rewarded 1300 ms later when a reward was associated with the green target (“green-reward block”), but neither was rewarded when a reward was associated with the yellow target (“yellow-reward block”). RT, reaction time; MT, movement time. (B) The two different roles alternated every two trials, and the color-reward contingency was switched every 5 to 17 trials (blocked design). N and E represent the actor in each trial. Trials with and without arrows indicate SWITCH and non-SWITCH trials, respectively.

  • Fig. 2 Animals’ selection behavior in different case scenarios.

    The percentage of correct choice in the current trial (n) is shown for each monkey in the rightmost column. Values on top of the bars represent the averages. Error bars denote SEM. In all the examples shown, the green target was initially associated with a reward (see the leftmost insets). (A) In the preceding trial (n − 1), the actor was either the partner (upper panel) or oneself (lower panel), and the actor’s selection was followed by a reward. The animal to be analyzed is designated as “self.” The correct target color in the trial (n) is indicated in parentheses. (B) In the preceding trial (n − 1), the actor was either the partner (upper panel) or oneself (lower panel), and the actor’s selection was followed by no reward owing to block switches. Other conventions are the same as in (A). (C) In the preceding trial (n − 1), the actor was either the partner (upper panel) or oneself (lower panel), and the actor’s selection was followed by no reward owing to a choice error. Other conventions are the same as in (A).

  • Fig. 3 T1-weighted magnetic resonance images for monkey E.

    Each coronal section was obtained at the rostrocaudal level indicated by a corresponding white line and lettering below. Each corresponding Horsley-Clarke stereotactic coordinate is also shown. A, anterior; P, posterior. Note that there was no gross structural abnormality.

  • Fig. 4 Three types of agent-related neuron in the MFC of monkey E.

    Raster displays and spike density functions of one example each of self-type neuron (top), mirror-type neuron (middle), and partner-type neuron (bottom). Small black dots indicate the time of individual action potentials; large black dots indicate the time of target button onset. The displays are aligned on the time of the actor’s target button pressing (vertical lines). See also fig. S4 for other examples recorded from the neurotypical monkeys.

  • Fig. 5 Rare deletion disrupting ABCA13 in monkey E.

    (A) Heterozygous ABCA13 deletion in monkey E (red bar). The coordinates of the deletion were chr3:77110419-78101380, as determined on the basis of the rhesus macaque (Macaca mulatta) genome assembly (rheMac2, January 2006). Gene annotation was taken from Ensembl Gene Predictions (Ensembl 76). Two Ensembl transcripts (ENSMMUT00000011190 and ENSMMUT00000042298) overlapping this deletion were derived from pseudogenes. (B) Log2 ratio plot of ABCA13 deletion. The data were obtained from aCGH results. (C) ABCA13 deletion in monkey E was validated by a real-time PCR-based TaqMan copy number assay. Bars indicate copy numbers predicted by this assay. Controls 1 to 4 carried no aCGH-detected CNVs at ABCA13 (copy number = 2).

  • Fig. 6 Nonsense mutation affecting HTR2C in monkey E.

    (A) Alignment of short-read sequences on HTR2C showing cytosine-to-thymine mutation. This mutation affected the truncated isoforms (HTR002_001: ENSMMUT00000013418), conferring nonsense mutation on this isoform. (B) Sanger-based sequencing for genotyping HTR2C mutation. PCR was performed in monkey E (top) and 10 other male monkeys as controls. The result indicates that only monkey E has the LoF mutation (C-to-T mutation) at the position of 113,403,559 on chromosome X, and all other control monkeys show wild-type genotypes at the same position. (C and D) Expression levels of two HTC2C isoforms in a series of developmental stages (C) and in different brain regions (D). Values in parentheses represent the number of samples. Error bars represent SEM. FPKM, fragments per kilobase of exon per million fragments mapped; BA46, Brodmann area 46; BA44, Brodmann area 44; ACC, anterior cingulate cortex; M1, primary motor cortex; S1, primary somatosensory cortex; TE, inferior temporal gyrus; V1, primary visual cortex; STR, striatum; TH, thalamus; SN, substantia nigra; HIP, hippocampus; CEC, cerebellum.

  • Table 1 Number of agent-related neurons in MFC.

    Values denote the number of neurons. Values in parentheses denote the percentage.

    Self-type neuronsMirror-type neuronsPartner-type neuronsTotal neurons recorded
    Monkey N60 (10.0)34 (5.7)101 (16.8)601
    Monkey S40 (15.3)26 (10.0)37 (14.2)261
    Monkey E49 (22.8)4 (1.9)5 (2.3)215

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/2/9/e1600558/DC1

    Supplementary Text

    fig. S1. Effects of outcomes in two trials before current choice.

    fig. S2. Animals’ gaze behavior.

    fig. S3. Animals’ RT analysis.

    fig. S4. Three types of agent-related neurons in the MFC.

    table S1. All CNVs detected in monkey E.

    table S2. All LoF mutations only identified in monkey E.

    References (59100)

  • Supplementary Materials

    This PDF file includes:

    • Supplementary Text
    • fig. S1. Effects of outcomes in two trials before current choice.
    • fig. S2. Animals’ gaze behavior.
    • fig. S3. Animals’ RT analysis.
    • fig. S4. Three types of agent-related neurons in the MFC.
    • table S1. All CNVs detected in monkey E.
    • table S2. All LoF mutations only identified in monkey E.
    • References (59100)

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