Biology subjects

Parra, S.

Publications and source records attributed to Parra, S..

3 recordsLinked to original sources

bioRxiv2022

Gain-of-function dynamin-2 mutations linked to centronuclear myopathy impair Ca2+-induced exocytosis in human myoblasts

Gain-of-function mutations of dynamin-2, a mechano-GTPase that remodels membrane and actin filaments, cause centronuclear myopathy (CNM), a congenital disease that mainly affects skeletal muscle tissue. Among these mutations, the variants p.A618T and p.S619L lead to gain of function and cause a severe neonatal phenotype. By using total internal reflection fluorescence microscopy (TIRFM) in immortalized human myoblasts expressing the pH-sensitive fluorescent protein (pHluorin) fused to the insulin-responsive aminopeptidase IRAP as reporter of the GLUT4 vesicle-trafficking, we measured single pHluorin signals to investigate how p.A618T and p.S619L mutations influence exocytosis. We show here that both dynamin-2 mutations significantly reduced the number and durations of pHluorin signals induced by 10 M ionomycin, indicating that in addition to impair exocytosis, they also affect the fusion pore dynamics. These mutations also disrupt the formation of actin filaments, a process that reportedly favors exocytosis. This altered exocytosis might importantly disturb the plasmalemma expression of functional proteins such as the glucose transporter GLUT4 in skeletal muscle cells, impacting the physiology of the skeletal muscle tissue and contributing to the CNM disease.

physiology↗

bioRxiv2022

An abstract categorical decision code in dorsal premotor cortex

The dorsal premotor cortex (DPC) has classically been associated with a role in preparing and executing the physical motor variables during cognitive tasks. While recent work has provided nuanced insights into this role, here we propose that DPC also participates more actively in decision-making. We recorded neuronal activity in DPC while two trained monkeys performed a vibrotactile categorization task, utilizing two distinct ranges of stimuli values that varied on two physical attributes: vibrotactile frequency and amplitude. We observed a broad heterogeneity across DPC neurons, the majority of which maintained the same response patterns across attributes and ranges, coding in the same periods, mixing temporal and categorical dynamics. The predominant categorical signal was maintained throughout the delay, movement periods and notably during the inter-trial period. Putting the entire populations data through two dimensionality reduction techniques, we found that imposing the sensory structure yielded pure categorical and temporal representations. Furthermore, projecting the activity of one population over the population axes of the other yielded identical categorical and temporal responses. Finally, we sought to identify functional subpopulations based on the combined activity of all stimuli, neurons, and time points, however we found a continuum of single-unit responses mixing temporal and categorical dynamics. All this points to DPC playing a more decision-related role than previously anticipated. SIGNIFICANCE STATEMENTThe DPCs role in the somatosensory processing network has been generally limited to movement, but our current results suggest a more abstract function. We recorded DPCs activity in two monkeys trained in a vibrotactile categorization task of two distinct physical attributes, and found a strong decision signal throughout the population, underpinned by purely temporal signals. Importantly, this abstract decision signal remains during the inter-trial period suggesting a consolidation role. Neurons maintained consistent and significant responses for both attributes, and the entire population activity converged to identical categorical representations, even when cross-projected between two contexts. These results suggest that DPC plays a larger role during decision-making and consolidation, regardless of the stimulus attributes that triggered the decision report.

neuroscience↗

bioRxiv2022

Hierarchical unimodal processing within the primary somatosensory cortex during a bimodal detection task

Where and how in the brain do neurons process more than one sensory modality? To answer these questions, scientists have generated a wide variety of studies at distinct space-time scales in different animal models, and often shown contradictory conclusions. Some conclude that this process occurs in early sensory cortices, but others that this occurs in areas central to sensory cortices. Here, we sought to determine whether sensory neurons process and encode physical stimulus properties of different modalities (tactile and acoustic). For this, we designed a bimodal detection task where the senses of touch and hearing compete from trial to trial. Two Rhesus monkeys performed this novel task, while neural activity was recorded in areas 3b and 1 of the primary somatosensory cortex (S1). We analyzed neurons coding properties and variability, organizing them by their receptive fields position relative to the stimulation zone. Our results indicate that neurons of areas 3b and 1 are unimodal, encoding only the tactile modality, both in the firing rate and variability, but not to the acoustic one. Moreover, we found that neurons of both subareas encode the tactile information differently, revealing a hidden processingbased hierarchy. Finally, using a powerful non-linear dimensionality reduction algorithm, we show that the activity from areas 3b and 1 can be separated, establishing a clear division in the functionality of these two subareas of S1. SIGNIFICANCE STATEMENTOur brain integrates information from all our senses to perceive the external world. But where and how in the brain this integration occurs? Here we ask if the primary somatosensory cortex (S1) encodes information from more than one sensory modality. We recorded the activity of single neurons from areas 3b and S1, while trained monkeys performed a bimodal detection task, where tactile and acoustic stimuli compete. The analysis showed that neurons from areas 3b and 1 responded only to the tactile modality both in their rate and variability. However, our results support that these two areas are different enough as to be considered functionally distinct entities.

neuroscience↗