Biology subjects

Modi, M.

Publications and source records attributed to Modi, M..

4 recordsLinked to original sources

bioRxiv2023

Stochastic coding: a conserved feature of odor representations and its implications for odor discrimination

Sparse coding is thought to improve discrimination of sensory stimuli by reducing overlap between their representations. Two factors, however, can offset sparse codings advantages. Similar sensory stimuli have significant overlap, and responses vary across trials. To elucidate the effect of these two factors, we analyzed odor responses in the fly and mouse olfactory regions implicated in learning and discrimination -- the Mushroom Body (MB) and the Piriform Cortex (PCx). In both species, we show that neuronal responses fall along a continuum from extremely reliable across trials to extremely variable or stochastic. Computationally, we show that the range of observed variability arises from probabilistic synapses in inhibitory feedback connections within central circuits rather than sensory noise, as is traditionally assumed. We propose this coding scheme to be advantageous for coarse- and fine-odor discrimination. More reliable cells enable quick discrimination between dissimilar odors. For similar odors, however, these cells overlap, and do not provide distinguishing information. By contrast, more unreliable cells are decorrelated for similar odors, providing distinguishing information, though this requires extended training with more trials. Overall, we have uncovered a stochastic coding scheme that is conserved in vertebrates and invertebrates, and we identify a candidate mechanism, based on variability in a winner-take-all inhibitory circuit, that improves discrimination with training.

neuroscience↗

bioRxiv2022

Vimentin supports directional cell migration by controlling focal adhesions

Persistent cell migration requires focal adhesions to assemble and disassemble locally while maintaining global front-rear alignment. The mechanism that enforces this long-range spatial coherence remains unresolved. Here we identify the intermediate filament protein vimentin as a cell-scale organizer that stabilizes focal adhesion alignment during directed fibroblast migration. Using quantitative live-cell imaging, we show that vimentin-deficient fibroblasts lose directional persistence and a complete collapse of global focal adhesion alignment. Quantitative analysis reveals that vimentin stabilizes focal adhesion alignment by constraining angular fluctuations and preserving the periodic bias of adhesion birth across the adhesion field. Loss of vimentin results in smaller, rapidly turning-over adhesions with disrupted orientation. Trajectory analysis reveals a mechanically anchored adhesion state selectively associated with vimentin recruitment, distinguishing mechanical stabilization from biochemical maturation. Super-resolution and iPALM imaging further show that vimentin integrates within the focal adhesion nanoarchitecture near the force-transduction layer. Together, our findings establish that vimentin intermediate filaments impose spatial coherence on adhesion dynamics, converting locally stochastic adhesion assembly, turnover, and disassembly into globally coordinated adhesions and persistent directional migration.

cell biology↗

bioRxiv2021

Cytoskeletal vimentin regulates cell size and autophagy through mTORC1 signaling

The nutrient-activated mTORC1 (mechanistic target of rapamycin kinase complex 1) signaling pathway determines cell size by controlling mRNA translation, ribosome biogenesis, protein synthesis, and autophagy. Here we show that vimentin, a cytoskeletal intermediate filament protein that we know to be important for wound healing and cancer progression, determines cell size through mTORC1 signaling, an effect that is also manifested at the organism level in mice. We found that vimentin maintains normal cell size by supporting mTORC1 activation and through inhibition of autophagic flux. This regulation is manifested at all levels of downstream target activation and regulation of protein synthesis. We show that vimentin controls mTORC1 mobility by allowing access to lysosomes. Vimentin inhibits the autophagic flux in normal fibroblasts even under starved conditions, indicating a growth factor-independent inhibition of autophagy at the level of mTORC1. Our findings demonstrate that vimentin couples cell size signaling and autophagy with the biomechanic, sensing, and kinetic functions of the cytoskeleton.

cell biology↗

bioRxiv2019

Two-photon Imaging with Silicon Photomultipliers

Silicon photomultipliers (SiPMs) are a class of inexpensive and robust single-pixel detectors with applications similar to photomultiplier tubes (PMTs). We performed side-by-side comparisons of recently-developed SiPMs and a GaAsP PMT for two-photon fluorescence imaging of neural activity. Despite higher dark counts, which limit their performance at low photon rates (<1s), SiPMs matched the signal-to-noise ratio of the GaAsP PMT at photon rates encountered in typical calcium imaging experiments due to their much lower pulse height variability. At higher photon rates and dynamic ranges encountered during high-speed two-photon voltage imaging, SiPMs significantly outperformed the GaAsP PMT.

neuroscience↗