Il Hwan Kim, Mark A Rossi, Dipendra K Aryal, Bence Racz, Namsoo Kim, Akiyoshi Uezu, Fan Wang, William C Wetsel, Richard J Weinberg, Henry Yin, Scott H Soderling
Abstract
Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, the actin-related protein 2/3 complex (Arp2/3), we report here a molecular mechanism that unexpectedly reveals the inter-relationship of progressive spine pruning, elevated frontal cortical excitation of pyramidal neurons and striatal hyperdopaminergia in a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, this antipsychotic-responsive locomotion can be mimicked in wild-type mice by optogenetic activation of this circuit. Collectively these results reveal molecular and neural-circuit mechanisms, illustrating how diverse pathologies may converge to drive behaviors relevant to psychiatric disorders.
This research output has an Altmetric Attention Score of 103. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 February 2022.
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#18
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Altmetric has tracked 24,877,044 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,530 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 55.9. This one has done well, scoring higher than 86% of its peers.
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We're also able to compare this research output to 69 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.
