Biology subjects

Coello, J. A.

Publications and source records attributed to Coello, J. A..

3 recordsLinked to original sources

bioRxiv2026

Cerebellar mitochondrial dysfunction coincides with structural and behavioral abnormalities in 3q29Del mice

3q29 deletion (3q29Del) is a genetic risk variant for autism spectrum disorder and schizophrenia that often results in developmental delays, cognitive disability, and impaired fine motor function. People with 3q29Del have reduced cerebellar volume, which correlates with symptom severity, and many 3q29Del-associated phenotypes also commonly occur after cerebellar injury or dysfunction. However, it is unknown whether the existing 3q29Del mouse model recapitulates the cerebellar dysfunction observed in humans. To characterize cerebellar phenotypes and uncover pathological differences in the 3q29Del mouse model, we investigated cerebellar structure, motor and vocal behaviors, protein expression, and mitochondrial function. We found uniformly reduced cerebellar volume in 3q29Del mice. Behavioral assays revealed vocal impairments in 3q29Del pups, fine motor impairments in adult mice, and reduced social mating calls in adult male mice. Proteomic analysis revealed enrichment of synaptic and mitochondrial proteins among the differentially expressed proteins in 3q29Del cerebellum tissue. Furthermore, mitochondria from 3q29Del mouse cerebellum displayed reduced oxygen flux and increased electron leak. These results recapitulate many human 3q29Del phenotypes in the 3q29Del mouse model and indicate mitochondrial dysfunction as a potential driver of 3q29Del pathology. Our findings also point to cerebellar involvement in 3q29Del phenotypes and provide a foundation for further research on cerebellar development in 3q29Del.

neuroscience↗

bioRxiv2026

Competitive Olivocerebellar Input Selection Promotes Resilient Circuit Formation

Many neural circuits undergo competitive input selection, a process in which supernumerary connections compete for innervation territory on target cells. This process can create atypical circuits when functional inputs are favored over compromised ones. Yet, it is often unclear whether such atypical circuits are maladaptive or promote functional resilience. We investigated this using the olivocerebellar climbing fiber circuit, where multiple inputs compete to mono-innervate Purkinje cells. We found that eliminating neurotransmission from [~]50% of olivocerebellar neurons reduced climbing fibers competitiveness during input selection and decreased survival of parental inferior olive neurons. Conversely, functional climbing fibers expanded their innervation territory. Despite these atypical circuits, climbing-fiber-dependent motor control was only minimally affected and social behaviors were fully preserved. These results demonstrate that neurotransmission-dependent competition promotes resilient circuits formation, maintaining complex behaviors even when a large proportion of inputs to the cerebellum are developmentally compromised.

neuroscience↗

bioRxiv2025

Modeling Laryngeal Dystonia through Spectral Analyses of Vocalizations in a Dystonia Mouse Model

Laryngeal dystonia is a task-specific, focal dystonia that disrupts vocal-motor control and significantly alters quality of life through impaired communication. Despite its early onset in many hereditary dystonias, effective treatments remain limited, in part due to the lack of a preclinical model that captures its circuit-level pathophysiology. Our experiment evaluates ultrasonic vocalizations (USVs) in Ptf1aCre/+;Vglut2fl/fl mice, a cerebellum-specific generalized dystonia model, to assess translational relevance for laryngeal dystonia. At postnatal day 9, mutant mice demonstrated statistically significant reductions in total USV count, relative count of complex calls, and key spectral parameters-- especially frequency modulation and power--mirroring phonatory abnormalities seen in human patients. Cluster analyses further revealed impaired vocal burst initiation, suggesting disrupted cerebellar coordination of temporal vocal-motor output. These findings support the models construct and face validity for cerebellar contributions to disordered phonation. By revealing these potential translational biomarkers, our study establishes a foundational platform for future mechanistic and interventional research in laryngeal dystonia. SUMMARY STATEMENTWe demonstrate that a cerebellar general dystonia mouse model recapitulates vocal-motor deficits seen in laryngeal dystonia, providing a foundational platform for mechanistic studies and translational therapeutic discovery.

neuroscience↗