Biology subjects

Chacon, C.

Publications and source records attributed to Chacon, C..

3 recordsLinked to original sources

bioRxiv2023

Lumbar locomotor-related V3 interneurons provide direct excitatory synaptic input onto thoracic sympathetic preganglionic neurons

Spinal cord injury (SCI) is a life-altering event causing sensation loss, motor paralysis and impaired autonomic function. Electrical spinal cord stimulation has shown promise for restoring lost motor, and impaired autonomic function, despite targeting lumbar locomotor networks. Sympathetic preganglionic neurons (SPNs), primarily located in the intermediate laminae of thoracic and upper lumbar segments (T1-L2), provide neural input to excite sympathetic tissues and organs that provide homeostatic and metabolic support during movement and exercise. We hypothesized that ascending propriospinal neurons located in the lumbar spinal cord provide synaptic input to thoracic SPNs, providing a spinal neural mechanism explaining improved motor and autonomic function in response to spinal cord stimulation. Here, we demonstrate that synaptic contacts from locomotor-related V3 interneurons (INs) are present in all thoracic laminae. Injection of an anterograde tracer into lumbar segments demonstrated that 8-20% of glutamatergic input onto SPNs originated from lumbar V3 INs and displayed a somatotopographical organization of synaptic input to thoracic SPNs, with rostral lumbar V3 INs projecting to rostral thoracic, and caudal lumbar V3 INs projecting to caudal thoracic SPNs. Whole cell patch clamp recording in SPNs demonstrated prolonged depolarizations or action potentials in response to optical activation of either lumbar V3 INs in spinal cord preparations or in response to optical activation of V3 terminals in thoracic slice preparations. This work demonstrates a direct intraspinal connection between lumbar locomotor and thoracic sympathetic networks and suggests communication between motor and autonomic systems may be a general function of the spinal cord. Key pointsO_LIWe provide direct anatomical and electrophysiological evidence of an ascending intraspinal synaptic connection between lumbar motor and thoracic sympathetic autonomic neural systems. C_LIO_LIThese connections are formed between lumbar locomotor related V3 interneurons and thoracic sympathetic preganglionic neurons (SPNs) C_LIO_LIV3 synaptic input accounts for [~] 20% of glutamatergic input to SPNs. C_LIO_LIOptical activation of lumbar V3 interneurons elicit action potentials in thoracic SPNs. C_LIO_LIThis intraspinal pathway may explain why electrical stimulation of the lumbar region in persons with long-standing motor complete spinal cord injury improves both motor and sympathetic function. C_LIO_LIThese findings suggest communication between motor and autonomic systems may be a general feature of spinal cord function and await further research to explore this concept. C_LI

neuroscience↗

bioRxiv2022

Schizophrenia-derived hiPSC brain microvascular endothelial cells show impairments in angiogenesis and blood-brain barrier function

Schizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed out a possible vascular deficiency that could be acting synergistically with neuronal dysfunction in SZ. As SZ is a neurodevelopmental disease, the use of human induced pluripotent stem cells (hiPSC) allows disease biology modeling retaining the patients unique genetic signature. Previously, we reported a VEGF-A signaling impairment in SZ-hiPSC derived neural lineages leading to a decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective Blood-Brain Barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BECs secretome reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis that traces schizophrenia origins to brain development and BBB dysfunction.

cell biology↗

bioRxiv2020

A first assessment of the distribution and abundance of large pelagic species at Cocos Ridge seamounts (Eastern Tropical Pacific) using drifting pelagic baited remote cameras

Understanding the link between seamounts and large pelagic species (LPS) is critical for guiding management and conservation efforts in open water ecosystems. The seamounts along the Cocos Ridge in the Eastern Tropical Pacific (ETP) are thought to play a critical role for LPS moving between Cocos Island (Costa Rica) and Galapagos Islands (Ecuador). However, to date, research efforts to understand pelagic community structure beyond the borders of these oceanic Marine Protected Areas (MPAs) have been limited. This study used drifting-pelagic baited remote underwater video stations (BRUVS) to characterize the distribution and relative abundance of LPS at Cocos Ridge seamounts. Our drifting-pelagic BRUVS detected a total of 21 species including sharks, large teleosts, small teleosts, dolphins and one sea turtle, of which 4 are threatened species. Relative abundance and richness of LPS was significantly higher at shallow seamounts (<400m) compared to deeper ones (>400m) suggesting that seamount depth could be an important driver structuring LPS assemblages along the Cocos Ridge. Our cameras provided the first visual evidence of the schooling behaviour of S. lewini at two shallow seamounts outside the protection limits of Cocos and Galapagos Islands. However, further research is still needed to demonstrate a positive association between LPS and Cocos Ridge seamounts. Our findings showed that drifting pelagic BRUVS are an effective tool to survey LPS in fully pelagic ecosystems of the ETP. This study represents the first step towards the standardization of this technique throughout the region.

ecology↗