# Typical and Pathological Cellular Development of the Human Amygdala

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $392,500

## Abstract

ABSTRACT
The amygdala has been implicated in a number of neurodevelopmental and psychiatric disorders, including
autism spectrum disorder (ASD). This is likely because it is part of a system focused on detecting danger in the
environment, processing cortical sensory input, and orchestrating subsequent responses. If this system
becomes dysfunctional, inappropriate social behavior or anxiety may arise, as is observed in many, often
debilitating, psychiatric disorders. Thus, treatment approaches may be facilitated by a precise understanding of
the amygdala cellular composition and developmental trajectory that occurs across human lifespan.
Considering impairments in social interaction and anxiety are key features of ASD, it is not surprising that the
amygdala has been extensively implicated in ASD pathophysiology. The overarching objective of our research
program is to reveal the cellular and molecular mechanisms underlying amygdala structure and function in
typical human development and in ASD across the lifespan. In the first funding cycle of this research program,
we discovered two phenomena through our studies of a large collection of human postmortem amygdala tissue
samples. First, in neurotypical human brain development, the amygdala undergoes a substantial, protracted
growth in both volume and in the number of mature neurons from youth well into adulthood. We hypothesize
that this is attributable to a prolonged process of neuronal maturation in the basal and paralaminar nuclei, and
that this protracted growth is critically important for normal social and emotional development. Second, in ASD
brain development, the amygdala does not undergo the same age-related growth trajectory. Rather, the
amygdala in ASD undergoes an aberrant, lifelong developmental time course that begins with premature
volumetric enlargement and an excess number of mature neurons and synaptic spines in childhood. In fact, the
number of mature neurons reaches adult levels by late childhood, suggesting that a preternatural neuronal
maturation process is occurring in the amygdala basal and paralaminar nuclei. Dendrites of principal excitatory
neurons in the amygdala of children with ASD also have an increase in spine density relative to neurotypical
children, indicating altered neuronal synaptic communication. This increase is followed by a potentially
degenerative cell loss as people with ASD age into adulthood. We have found that there is a steady decrease
across age in the number of mature neurons in both the lateral and basal nucleus in adults with ASD relative to
neurotypical adults. We hypothesize that hyperactivity and excitation in the amygdala, via an imbalance of
excitatory to inhibitory (E:I) synaptic signaling, potentially contributes to anxiety, social impairments, and
prospective neuron loss. We now move to the next phase of this research program, to identify specific
neuronal properties and pathophysiological mechanisms that underlie the atypical amygdala cell...

## Key facts

- **NIH application ID:** 10168614
- **Project number:** 5R01MH097236-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Cynthia Schumann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2011-09-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168614

## Citation

> US National Institutes of Health, RePORTER application 10168614, Typical and Pathological Cellular Development of the Human Amygdala (5R01MH097236-09). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10168614. Licensed CC0.

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