Amygdala Neuron Numbers Decline Into Adulthood In Autism

Typically-developing children gain more neurons in a region of the brain that governs social and emotional behavior, the amygdala, as they become adults, researchers at the UC Davis MIND Institute have found.

Additionally, this phenomenon does not happen in people with autism spectrum disorder (ASD). Instead, children with ASD have too many neurons early on and then appear to lose those neurons as they become adults.

The amygdala is a small almond-shaped group of 13 regions (nuclei) that work as a danger detector in the brain to regulate anxiety and social interactions. Amygdala dysfunction has been linked to many psychiatric and neurodevelopmental disorders, including ASD, schizophrenia, bipolar disorder and depression.

Amygdala Development

Cynthia Schumann, associate professor in the Department of Psychiatry and Behavioral Sciences at the UC Davis MIND Institute and senior author of the paper, said:

“The amygdala is a unique brain structure in that it grows dramatically during adolescence, longer than other brain regions, as we become more socially and emotionally mature. Any deviation from this normal path of development can profoundly influence human behavior.”

To understand what cellular factors underlie amygdala development, the team studied 52 postmortem human brains, both neurotypical and ASD, ranging from 2 to 48 years of age.

“We were surprised to find that the number of neurons in one of the amygdala regions increased by more than 30% from childhood to adulthood in typically-developing individuals,”

said Schumann.

A methodological summary of the stereological approach.

A methodological summary of the 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.
Credit: Thomas A. Avino, et al. CC-BY

Too Many Neurons?

The picture was quite different in people with ASD. There were more neurons in young children with ASD, but as they got older, those numbers went down.

“We don’t know if having too many amygdala neurons early in development in ASD is related to the apparent loss later on,” said Schumann. “It’s possible that having too many neurons early on could contribute to anxiety and challenges with social interactions. However, with time, that constant activity could wear on the system and lead to neuron loss.”

Schumann and her team believe that if they can explain how the cells are changing throughout adolescence in the amygdala, it might be possible to intervene and treat symptoms such as anxiety that develop in people with autism and other neurodevelopmental and psychiatric disorders.

The work was supported by grants form the NIH. Tissue samples were provided by Autism BrainNet, supported by the Simons Foundation (formerly the Autism Tissue Program with Dr. Jane Pickett, supported by Autism Speaks) and the NIH NeuroBioBank at the University of Maryland Brain and Tissue Bank with Dr. Ron Zielke.

Thomas A. Avino, Nicole Barger, Martha V. Vargas, Erin L. Carlson, David G. Amaral, Melissa D. Bauman, Cynthia M. Schumann
Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism
Proceedings of the National Academy of Sciences Mar 2018, 201801912; DOI: 10.1073/pnas.1801912115

Top Image: Amber Rieder, Jenna Traynor, Geoffrey B Hall