Authors:

Daisy Maturo

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About Paper:

Autism Spectrum Disorder (ASD) is a complex, multigenic neurodevelopmental disorder that affects 1 in 36 people in the United States. ASD is characterized by differences in sensory processing and brain connectivity, which are thought to stem from disruptions in axon guidance and circuit formation. A neuron's morphology is postulated to be essential for proper circuit formation as it directly impacts its ability to form physical connections with other neurons, thus influencing connectivity. Our research aims to link changes in neuron morphology to disruptions in brain circuit wiring using a conditional deletion model of a clinically-relevant ASD gene in cortical pyramidal neurons. We employed genetic reporters to sparsely label neuron morphologies alongside a thalamocortical axon (TCA) reporter to visualize incoming circuits. Using Neurod6-cre to drive postmitotic deletion of our gene of interest specifically from cortical pyramidal neurons, we analyzed layer-specific neuron morphologies and compared TCA development in control and conditional knockout (cKO) mice via immunostaining and confocal imaging. Our analysis revealed that the morphologies of pyramidal neurons in cKO cortex were disrupted, with differences in polarity and less elaborate dendrites compared to controls. Interestingly, this change in morphology was accompanied by misrouting of TCAs and their failure to organize into distinct barrels within the somatosensory cortex of cKO mice. Additionally, we observed a reduction in the thickness of the upper layers of the cortex, which may be due to the observed reduction of dendritic branching. Together, these findings suggest that the acquisition of correct pyramidal neuron morphologies is essential for directing axonal connectivity, providing a potential cellular mechanism for the disrupted brain wiring seen in ASD.

Source:

Chicago Area Undergraduate Research Symposium

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Co-authors:

Daisy Maturo