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. 2018 Apr 3;115(14):3710-3715.
doi: 10.1073/pnas.1801912115. Epub 2018 Mar 20.

Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism

Thomas A Avino  1 , Nicole Barger  1 , Martha V Vargas  1 , Erin L Carlson  1 , David G Amaral  1   2   3 , Melissa D Bauman  1   2 , Cynthia M Schumann  4
Affiliations

Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism

Thomas A Avino et al. Proc Natl Acad Sci U S A. .

Abstract

Remarkably little is known about the postnatal cellular development of the human amygdala. It plays a central role in mediating emotional behavior and has an unusually protracted development well into adulthood, increasing in size by 40% from youth to adulthood. Variation from this typical neurodevelopmental trajectory could have profound implications on normal emotional development. We report the results of a stereological analysis of the number of neurons in amygdala nuclei of 52 human brains ranging from 2 to 48 years of age [24 neurotypical and 28 autism spectrum disorder (ASD)]. In neurotypical development, the number of mature neurons in the basal and accessory basal nuclei increases from childhood to adulthood, coinciding with a decrease of immature neurons within the paralaminar nucleus. Individuals with ASD, in contrast, show an initial excess of amygdala neurons during childhood, followed by a reduction in adulthood across nuclei. We propose that there is a long-term contribution of mature neurons from the paralaminar nucleus to other nuclei of the neurotypical human amygdala and that this growth trajectory may be altered in ASD, potentially underlying the volumetric changes detected in ASD and other neurodevelopmental or neuropsychiatric disorders.

Keywords: amygdala; autism; neuroanatomy; neuronal maturation; stereology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Mature neuron number across amygdala nuclei between ASD and NT subjects. Young subjects with ASD show an increased number of mature neurons relative to NT subjects (in total amygdala, basal, accessory basal, and central nuclei). By adulthood, the number of mature neurons in ASD is well below the adult NT average in every nucleus examined (17%). Error bars ±1 SEM. When considering the monkey basal + paralaminar nuclei (6) as a single unit (as we have done with the human basal nucleus, Lower Right), there is a comparable increase of mature neurons (∼32%) across life between the two species.
Fig. 2.
Fig. 2.
The paralaminar nucleus in a Nissl-stained section (A) relative to a bcl-2–stained section from a 2-y-old NT subject (B) and a 44-y-old NT subject (C) showing age-related differences. The immature neuron morphology for each is shown in their respective Insets. (D) Stereological assessment of bcl-2+ between ASD and NT groups from individuals aged 2 to 44 y showing an age-related decline of bcl-2+ cells in both groups across the life span. (E and F) Bcl-2 sections from a 5-y-old ASD subject (E) and a 36-y-old ASD subject (F) showing similar staining patterns relative to NT subjects. (G) A bcl-2–stained fiber upon which immature neurons appear to migrate. (H and I) DCX-stained sections from the same two subjects as in B and C showing similar patterns of immunoreactivity with bcl-2. (Scale bars: A = 500 µm, Inset = 10 µm; B and C = 100 µm, Insets = 10 µm; E, F, H, and I = 100 µm; G = 25 µm.)
Fig. 3.
Fig. 3.
A methodological summary of our stereological approach. The entire rostrocaudal extent of the amygdala is sectioned. For experiment 1, we used Nissl-stained sections at a 1/5 sampling interval, and for experiment 2, we used alternating bcl-2–stained sections at a 1/10 sampling interval from the same brains. Each section has a virtual grid overlaid on top which designates physical locations to place sampling boxes. The numbers of objects are counted in each sampling box, and an estimate is extrapolated based on the size of the sampling box, the density of the sampling grid, the number of sections examined, and tissue thickness. Stereological parameters are presented in Table S2. (Scale bars: Left four, 2 mm; Right two, 10 µm.)
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References

    1. Adolphs R. What does the amygdala contribute to social cognition? Ann N Y Acad Sci. 2010;1191:42–61. - PMC - PubMed
    1. Fox AS, Oler JA, Tromp PM, Fudge JL, Kalin NH. Extending the amygdala in theories of threat processing. Trends Neurosci. 2015;38:319–329. - PMC - PubMed
    1. Amaral DG. The primate amygdala and the neurobiology of social behavior: Implications for understanding social anxiety. Biol Psychiatry. 2002;51:11–17. - PubMed
    1. Giedd JN, et al. Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: Ages 4-18 years. J Comp Neurol. 1996;366:223–230. - PubMed
    1. Schumann CM, et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci. 2004;24:6392–6401. - PMC - PubMed

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