Search bioRxiv⌕ Search

Biology subjects

Dmytriyeva, O.

Publications and source records attributed to Dmytriyeva, O..

3 recordsLinked to original sources

Cue-guided performance is disrupted during pedunculotegmental-induced motor arrest

Optogenetic stimulation of the rostral pedunculotegmental nucleus (PTg) induces global motor arrest, but it remains unclear whether this is merely a suppression of motor activity or a broader disruption of brain processes required to guide action. We developed a visuospatial cue task for rats, to test if sensory information presented during PTg-induced arrest can guide later responses. Here, we show that optogenetic stimulation during cue presentation reduces accuracy to chance level. By moving stimulation to only before or only after the cue, we found that performance was only affected when stimulation and cue presentation overlapped, that rats recover cue-guided behavior almost immediately at the end of stimulation, and that stimulation does not appear to abolish responses based on cue information acquired before arrest. These findings indicate that stimulation of the rostral PTg does not only pause motor output but transiently disrupts the ability to process and use cue information effectively.

neuroscience↗

Proteomic and phospho-proteomic longitudinal signatures of human skeletal muscle in lung cancer cachexia

Weight loss is a potentially deadly hallmark of many cancers, including lung cancer. In particular, the loss of skeletal muscle mass and function impairs survival and lowers quality of life. Despite being a major determinant of prognosis, the molecular drivers of muscle wasting remain ill-defined. Therefore, there is a critical need for human molecular data to support the development of effective therapies for this currently untreatable condition. Here, we utilize cutting-edge proteomics technology to longitudinally map the proteome and phosphoproteome of skeletal muscle from patients with newly diagnosed, advanced-stage non-small cell lung cancer during their treatment. Leveraging deep in vivo clinical phenotyping of activity, body composition, muscle quality, and nutritional risk, we identified 118/174 muscle proteins/phospho-sites associated with cachexia at diagnosis with indications of sexual dimorphism. Treatment altered 278 proteins and 1,155 phospho-sites, of which 137/91 proteins/phospho-sites were associated with muscle wasting. Our findings highlight disrupted calcium, anabolic, and stress signalling, alongside extracellular matrix and mitochondrial alterations, as key molecular features of cachexia in non-small cell lung cancer. These clinically anchored proteomic and phosphoproteomic signatures provide potential targets for future research.

molecular biology↗

Arrest of movement induced by Pedunculopontine-stimulation obstructs hippocampal theta rhythm

Complete movement arrest has recently been reported to be induced in rodents by optogenetic stimulation of a subpopulation within the pedunculopontine nucleus (PPN). This evoked arrest appears conspicuously similar to freezing behavior often seen as a fear response in prey animals but could also be akin to the freezing of gait, which is a symptom of Parkinsons disease. This introduces two perspectives on the functional roles of this sub-region: A hub for orchestrating fear-related responses or an omnipotent halting mechanism devoid of emotional components. To better understand this phenomenon and its cognitive component, we engage the distinct electrical brain activity, the hippocampal theta rhythm. This rhythm has a well-described contextual association between various aspects of cognition and behavior. It is prominent during locomotor activity in rodents and immobile yet aroused states like behavioral freezing. We recorded the electrical activity in the hippocampus of rats while walking and being arrested by PPN stimulation. A clear obstruction of the ongoing theta activity was associated with the motor arrest. The timescale of movement arrest was less than 200 ms, similar to the obstruction of the theta rhythm. Since, anxiety, fear, and behavioral freezing are associated with hippocampal theta rhythm, which we did not see during PPN stimulation, we suggest the induced motor arrest occurs without an associated emotional component.

neuroscience↗