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Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism

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A Developmental Neuroimmune Cascade Model of Autism Spectrum Disorder.

Gerry Leisman^1,2, Robert Melillo^1,3, Rahela Alfasi^1,3

¹Movement and Cognition Laboratory, Department of Physical Therapy, University of Haifa, Haifa 3498838, Israel.

International Journal of Molecular Sciences

|June 26, 2026

Summary

This summary is machine-generated.

A new model suggests early immune issues, interacting with genetics, may shape brain development in autism spectrum disorder (ASD). This neuroimmune cascade influences neural circuits and network function, impacting social cognition and sensory processing.

Keywords:

autism brain functional connection immune dysregulation insula maturation neuroimmunity neurotransmitters

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Area of Science:

Neuroscience
Immunology
Developmental Biology

Background:

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial origins.
Existing research on ASD's biological underpinnings is fragmented across different levels of analysis.
The interplay between immune processes and neurodevelopment in ASD requires a cohesive framework.

Purpose of the Study:

To propose a developmental neuroimmune cascade model for understanding ASD.
To integrate evidence from molecular, cellular, and systems levels concerning immune involvement in ASD.
To provide a structured basis for future research on neuroimmune mechanisms in ASD.

Main Methods:

Synthesized evidence from human observational studies, postmortem analyses, and animal models.
Examined immune-related mechanisms contributing to neurodevelopmental trajectories in ASD.
Distinguished associative findings from mechanistic inferences regarding immune factors.

Main Results:

Early-life immune perturbations, interacting with genetic susceptibility, can influence key neurodevelopmental processes.
These processes include cytokine signaling, microglial function, blood-brain barrier integrity, and gut-immune communication.
Altered neuroimmune pathways may affect synaptic pruning, excitatory-inhibitory balance, and neural circuit maturation, impacting brain networks involved in cognition and behavior.

Conclusions:

The proposed developmental neuroimmune cascade model offers a framework for understanding ASD heterogeneity.
Neuroimmune processes act as modulators of developmental trajectories rather than singular causes of ASD.
Findings have implications for developing biomarkers and stratified interventions, emphasizing developmental timing and biological diversity.