The study investigates how loss of the autism spectrum disorder (ASD) risk gene Cntnap2 impacts striatal neuron function and behavior in mice. The key findings are:
Striatal projection neurons (SPNs) in the direct and indirect pathways exhibit increased cortical drive in Cntnap2-/- mice, despite no changes in excitatory or inhibitory synaptic inputs.
The increased cortical drive onto SPNs is likely due to enhanced intrinsic excitability of these neurons, particularly in direct pathway SPNs.
Cntnap2-/- mice exhibit increased repetitive behaviors, including spontaneous grooming, marble burying, and nose poking in the holeboard assay.
Cntnap2-/- mice show enhanced motor learning on the accelerating rotarod task, which is associated with increased activity in the dorsolateral striatum.
Cntnap2-/- mice exhibit cognitive inflexibility, as demonstrated by impaired performance in an odor-based reversal learning task. This is characterized by perseverative errors, where the mice continue to choose the previously rewarded odor.
The authors propose that the increased intrinsic excitability and cortical drive of striatal projection neurons, particularly in the direct pathway, may contribute to the manifestation of repetitive behaviors and cognitive inflexibility in this mouse model of ASD.
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by Cording,K. R... lúc www.biorxiv.org 05-09-2024
https://www.biorxiv.org/content/10.1101/2024.05.09.593387v1Yêu cầu sâu hơn