Biology subjects

Salido, E. M.

Publications and source records attributed to Salido, E. M..

3 recordsLinked to original sources

bioRxiv2023

Intralimb locomotor coordination in rats walking on asymmetric pegway

Complex movements such as walking or reaching are generated by a sequence of muscle actions. How these coordinated actions subserve complex movements and their recovery after disruption remains unknown. The use of high throughput recording-stimulation systems with microelectrode access to structures along the neuraxis may complement the neurological models in rodents. To this purpose, we have trained rats to perform the precise foot placement locomotor task that allows us to assess skilled locomotor movements. Animals were pretrained on the peg walkway task, which was configured to impose either symmetric or asymmetric (with overstepping) locomotor stepping at preferred stride length. Selected forelimb muscles were implanted with intramuscular differential electrodes. After a week of recovery, we collected electromyography from the implanted muscles and ground reaction forces from the array of force sensors embedded into walkway pegs. The temporal relationship between muscle bursts was measured for each intralimb set of muscles (n=13) in symmetric and asymmetric stepping. The sequence corresponded to the progression of muscle actions responsible for limb lift, flexion and transport, overground clearance, and preparation for ground contact. The stereotyped spatiotemporal sequence of muscle activity was persistent and mirroring across the asymmetric tasks. These patterns are similar to those observed in cats during locomotion with and without obstacles and reaching movements. These findings support the hypothesis that the profiles of muscle activations are qualitatively similar across quadrupeds during precise locomotor tasks. New and NoteworthyWe characterize for the first time the spatiotemporal muscle activation in rat forelimb during precise asymmetric stepping on asymmetrically placed rungs. Similar to cats, the intralimb pattern of muscle activation in rats was stereotypical. The elements of this pattern were changing in a lateralized fashion based on the direction of the imposed asymmetry. The similarity of pattern to that of cats supports the idea of similarity of neural control across cat and rat species.

neuroscience↗

bioRxiv2022

Interphotoreceptor matrix proteoglycans IMPG1 and IMPG2 proteolyze in the SEA domain and reveal localization mutual dependency

The interphotoreceptor matrix (IPM) is a specialized extracellular mesh of molecules surrounding the inner and outer segments of photoreceptor neurons. Interphotoreceptor matrix proteoglycan 1 and 2 (IMPG1 and IMPG2) are major components of the IPM. Both proteoglycans possess SEA (sperm protein, enterokinase and agrin) domains, which may support proteolysis. Interestingly mutations in the SEA domains of IMPG1 and IMPG2 are associated with vision disease in humans. However, if SEA domains in IMPG molecules undergo proteolysis, and how this contributes to vision pathology is unknown. Therefore, we investigated SEA-mediated proteolysis of IMPG1 and IMPG2 and its significance to IPM physiology. Immunoblot analysis confirmed proteolysis of IMPG1 and IMPG2 in the retinas of wildtype mice. Point mutations mimicking human mutations in the SEA domain of IMPG1 that are associated with vision disease inhibited proteolysis. These findings demonstrate that proteolysis is part of the maturation of IMPG1 and IMPG2, in which deficits are associated with vision diseases. Further, immunohistochemical assays showed that proteolysis of IMPG2 generated two subunits, a membrane-attached peptide and an extracellular peptide. Notably, the extracellular portion of IMPG2 trafficked from the IPM around the inner segment toward the outer segment IPM by an IMPG1-dependent mechanism. This result provides the first evidence of a trafficking system that shuttles IMPG1 and IMPG2 from the inner to outer IPM in a co-dependent manner. In addition, these results suggest an interaction between IMPG1-IMPG2, and propose that mutations affecting one IMPG could affect the localization of the normal IMPG partner contributing to the disease mechanism of vision diseases associated with defective IMPG molecules.

molecular biology↗

bioRxiv2019

Proteoglycan IMPG2 shapes the interphotoreceptor matrix and modulates vision

The extracellular matrix surrounding the photoreceptor neurons, interphotoreceptor matrix (IPM) is comprised of two unique proteoglycans: IPM proteoglycan 1 and 2 (IMPG1 and IMPG2). Although the functions of the IPM are not understood, patients with mutations in IMPG1/2 develop visual deficits with subretinal material accumulation. Here, we generated mouse models lacking IMPG1/2 to decipher the role of these proteoglycans and the pathological mechanisms that lead to vision loss. IMPG1 and IMPG2 occupy specific locations in the outer retina, and both proteoglycans are fundamental for the constitution of the IPM system. Mice lacking IMPG2 show abnormal accumulation of IMPG1, and in later stages, develop subretinal lesions and reduced visual function. Interestingly, removal of IMPG1-2 showed normal retinal morphology and function, suggesting that the aberrant localization of IMPG1 causes the alterations observed in IMPG2 KO mice. In conclusion, our results demonstrate the role of IMPG2 in shaping the IPM, shed light on the potential mechanisms leading to subretinal lesions, and show that the secreted proteoglycans depend on the extracellular matrix environment to properly integrate into the matrix.

cell biology↗