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Published on: September 16, 2015
An indirect route to repetitive actions.
The Journal of Clinical Investigation
|April 18, 2017
Summary
Genetic links to autism spectrum disorders (ASDs) and repetitive behaviors were explored. Researchers found that a defective SHANK3B protein weakens synaptic transmission in the brain, leading to repetitive actions in mice, suggesting a potential therapeutic target.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Autism spectrum disorders (ASDs) and related neural disorders often involve genetic factors and repetitive behaviors.
- Postsynaptic scaffolding proteins, crucial for synaptic transmission and plasticity, are implicated in these conditions.
- Alterations in striatal synaptic transmission are observed in mouse models with mutations linked to ASDs.
Purpose of the Study:
- To investigate the role of the SHANK3B scaffolding protein in synaptic function within the striatum.
- To determine the impact of SHANK3B deficiency on neuronal pathways associated with repetitive behaviors.
- To explore the therapeutic potential of modulating striatal pathways for ASDs.
Main Methods:
- Studied mutant mice lacking the SHANK3B protein.
- Assessed glutamatergic synaptic transmission onto striatal projection neurons.
- Examined dendritic spine density on medium spiny projection neurons.
- Manipulated activity in the striatal indirect pathway.
Main Results:
- Mutant mice lacking SHANK3B showed weakened glutamatergic synaptic transmission onto striatal projection neurons.
- This resulted in increased activity in the indirect pathway and reduced dendritic spines on indirect pathway neurons.
- Enhancing activity in the indirect pathway decreased excessive repetitive grooming in mutant mice.
- Similar glutamatergic input changes were noted in other ASD models.
Conclusions:
- Defective SHANK3B impairs glutamatergic synaptic transmission in the striatum, contributing to repetitive behaviors.
- The striatal indirect pathway is a potential therapeutic target for disorders characterized by excessive repetitive actions.
- Further research into SHANK3B and striatal pathway modulation may offer new treatment strategies for ASDs.
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