Cited by 35Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchNeuroscience and Neuropharmacology Research

Synaptic structural protein dysfunction leads to altered excitation inhibition ratios in models of autism spectrum disorder

Howell, Brian W., Smith, Kathleen M.·2019·Pharmacological Research

Abstract

Genetics is believed to play a key role in the development of Autism Spectrum Disorder (ASD) and a plethora of potential candidate genes have been identified by genetic characterization of patients, their family members and controls. To make sense of this information investigators have searched for common pathways and downstream properties of neural networks that are regulated by these genes. For instance, several candidate genes encode synaptic proteins, and one hypothesis that has emerged is that disruption of the synaptic excitation and inhibition (E/I) balance would destabilize neural processing and lead to ASD phenotypes. Some compelling evidence for this has come from the analyses of mouse and culture models with defects in synaptic structural proteins, which influence several aspects of synapse biology and is the subject of this review. Remaining challenges include identifying the specifics that distinguish ASD from other psychiatric diseases and designing more direct tests of the E/I balance hypothesis.

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Crossref · 10.1016/j.phrs.2018.11.019

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Authors
Howell, B. W., & Smith, K. M.
Affiliations
SUNY Upstate Medical University (US)
Corresponding author
Howell, Brian W.
Venue
Pharmacological Research
Publisher
Elsevier BV
Published
2019-01
Volume
139
Pages
207-214
ISSN
1043-6618 (ISSN-L)
OpenAlex
W2901950380
Cited by
35
References
122
Citations by year
2026: 6 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 6
FWCI
0.55
Type
journal article
Language
en
Open access
closed
Locations
  • Pharmacological Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
autism spectrum disorder, excitation-inhibition balance, synaptic dysfunction, candidate genes, mouse model, cultural models, neural network stability
MeSH terms
Autism Spectrum Disorder, Animals, Humans, Membrane Proteins, Synapses, Intracellular Signaling Peptides and Proteins

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