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Bennett, M. A.

Publications and source records attributed to Bennett, M. A..

2 recordsLinked to original sources

Backward masking reveals coarse-to-fine dynamics in human V1

Natural images exhibit luminance variations aligned across a broad spectrum of spatial frequencies (SFs). It has been proposed that, at early stages of processing, the coarse signals carried by the low SF (LSF) of the visual input are sent rapidly from primary visual cortex (V1) to ventral, dorsal and frontal regions to form a coarse representation of the input, which is later sent back to V1 to guide the processing of fine-grained high SFs (i.e., HSF). We used functional resonance imaging (fMRI) to investigate the role of human V1 in the coarse-to-fine integration of visual input. We disrupted the processing of the coarse and fine content of full-spectrum human face stimuli via backward masking of selective SF ranges (LSFs: <1.75cpd and HSFs: >1.75cpd) at specific times (50, 83, 100 or 150ms). In line with coarse-to-fine proposals, we found that (1) the selective masking of stimulus LSF disrupted V1 activity in the earliest time window, and progressively decreased in influence, while (2) an opposite trend was observed for the masking of a stimulus HSF. This pattern of activity was found in V1, as well as in ventral (i.e. the Fusiform Face area, FFA), dorsal and orbitofrontal regions. We additionally presented participants with contrast negated stimuli. While contrast negation significantly reduced response amplitudes in the FFA, as well as coupling between FFA and V1, coarse-to-fine dynamics were not affected by this manipulation. The fact that V1 response dynamics to strictly identical stimulus sets differed depending on the masked scale adds to growing evidence that V1 role goes beyond the early and quasi-passive transmission of visual information to the rest of the brain. It instead indicates that V1 may yield a spatially registered common forum or blackboard that integrates top-down inferences with incoming visual signals through its recurrent interaction with high-level regions located in the inferotemporal, dorsal and frontal regions.

neuroscience↗

Smooth Muscle Myosin 2 Filaments Dynamically Assemble and Stabilize During Induced Contractility

BackgroundVascular smooth muscle cells (SMCs) dynamically tune blood vessel diameter to regulate blood pressure, provide vessel wall structural integrity, and absorb shock on a beat-to-beat timescale. Smooth muscle myosin 2 (SMII) is the dominant motor protein driving SMC contraction. To function, SMII monomers dynamically assemble into filaments, which associate with the actin cytoskeleton to drive contractility. Precisely how SMII filaments assemble and exchange in living SMCs, however, both at steady-state and during induced contractility, remains poorly defined. MethodsWe used a single-cell filament assembly assay to determine SMII assembly into filaments at steady-state and upon induced contractility in rat aortic SMCs (A7R5) transiently-expressing EGFP-tagged SM1A isoform of SMII. We then used fluorescence recovery after photobleaching (FRAP) to characterize SMII exchange kinetics at steady-state and upon induced contractility, and measured changes in force production using traction force microscopy. Finally, we developed a CRISPR knock-in EGFP-SMII murine model to quantify SMII dynamics at endogenous expression in primary SMCs and intact arterioles. ResultsWhile predominantly filamentous at baseline, induced contraction rapidly increased SMII filament assembly. FRAP revealed rapid SMII exchange kinetics, more similar to non-muscle myosin II than striated myosin II, and induced contractility consistently stabilized SMII filaments. Super-resolution imaging revealed SMII and non-muscle myosin II filament structures consistent with co-assembly. Endogenous EGFP-SMII in primary SMCs and intact arterioles paralleled cell culture studies with similar baseline exchange kinetics and activation-dependent stabilization. ConclusionsTogether, these data support a model in which SMII is surprisingly dynamic and co-assembles with non-muscle myosin II. Vascular SMC activation further increases SMII filament assembly while reducing filament exchange, consistent with stabilization of a dynamic SMII pool during force generation, which allows cells to dynamically adapt their overall contractility in response to environmental conditions. CLINICAL IMPLICATIONSSmooth muscle myosin II (SMII) is the principal contractile motor protein of vascular smooth muscle tissue, but its molecular behavior in living differentiated SMCs remains poorly defined. Here, we show that SMII is not a static contractile scaffold but highly dynamic. SMII exhibits dynamic exchange between the filament and monomeric forms at baseline, but becomes acutely stabilized during agonist-induced contraction, including in primary SMCs and intact arterioles at endogenous Myh11 expression. These findings suggest that vascular tone is tuned not only by activating pre-existing myosin filaments, but also by rapidly shifting SMII filament assembly levels and exchange rates. This framework is relevant to diseases in which SMC contractility and arterial wall mechanics are abnormal, including MYH11-associated thoracic aortic disease and related disorders of arterial stiffness or maladaptive vasomotor regulation. Although this study is mechanistic, it identifies SMII filament dynamics as a measurable layer of vascular regulation and a potential readout for future studies of pathogenic MYH11 variants, disease modeling, and therapies that alter myosin activation and/or cytoskeletal stability. O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/511341v2_ufig1.gif" ALT="Figure 1"> View larger version (78K): org.highwire.dtl.DTLVardef@d64a8forg.highwire.dtl.DTLVardef@b9000corg.highwire.dtl.DTLVardef@1b24a91org.highwire.dtl.DTLVardef@3d81be_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗