Biology subjects

Tohidi, S.

Publications and source records attributed to Tohidi, S..

3 recordsLinked to original sources

bioRxiv2025

Cortical GABAergic inhibition dynamics around hippocampal sharp-wave ripples

Hippocampal sharp-wave ripples (SWRs) coordinate hippocampal-neocortical interactions for memory consolidation, yet how cortical GABA signaling is organized around SWRs remains unclear. Here we approach this problem by combining wide-field mesoscale imaging of extracellular GABA using iGABASnFR2 with simultaneous dorsal CA1 electrophysiology and sleep-state monitoring in mice, enabling GABA dynamics to be mapped across 17 cortical regions during natural sleep and wakefulness. Using ripple-triggered activity mapping and singular value decomposition, we identified a cortex-wide GABA response consisting of a dominant global component and regionally structured components that were reconfigured across brain states. Across cortical subnetworks, SWRs were associated with a reduction in GABA signaling followed by widespread activation, with both components enhanced during NREM sleep. During NREM sleep, GABA responses emerged earliest and most strongly in the retrosplenial and other medial cortical regions before progressing laterally. During wakefulness, responses were faster, preferentially recruited lateral sensory regions and progressed towards medial cortex. Transitions between NREM sleep, REM sleep and wakefulness were also accompanied by distinct changes in GABA signaling and interregional network organization. Our findings suggest a model in which hippocampal SWRs recruit a shared cortex-wide GABA response whose regional expression and direction of propagation are reconfigured by brain state, providing a dynamic inhibitory framework for regulating hippocampal-neocortical communication.

neuroscience↗

bioRxiv2025

Characterization of iGABASnFR2 for in vivo mesoscale imaging of intracortical GABA dynamics

While genetically encoded sensors have advanced the study of cortical excitation, tools for large-scale imaging of inhibition remain limited. Visualizing extracellular GABA dynamics in vivo is essential for understanding how inhibitory networks shape brain activity across sensory, behavioral, and pharmacological states. To validate and apply the genetically encoded sensor iGABASnFR2 for wide-field imaging of extracellular GABA, and to characterize how cortical inhibition reorganizes across brain states, sensory modalities, and after GABA transporter blockade. We performed mesoscale imaging in head-fixed C57BL/6 mice systemically expressing iGABASnFR2. Recordings were conducted under isoflurane anesthesia, during quiet wakefulness, natural sleep (NREM and REM), and after administration of the GAT-1 inhibitor Tiagabine. We analyzed both sensory-evoked and spontaneous GABA signals using time-series, spectral, and seed-pixel correlation analyses. iGABASnFR2 demonstrated strong and modality-specific GABAergic responses to sensory stimulation, with faster and stronger activation in the contralateral cortex. Although the general spatial patterns of sensory-evoked GABA responses were consistent across anesthesia and quiet wakefulness, the amplitude, timing, and spread of these responses were significantly greater during wakefulness. During spontaneous activity, cortical GABA levels and connectivity modulated by brain state: GABA amplitude and interhemispheric synchrony were highest during quiet wakefulness but reduced during NREM sleep. Tiagabine elevated baseline GABA levels, abolished stimulus-evoked responses, and enhanced local and long-range inhibitory synchrony. iGABASnFR2 enables reliable, high-resolution imaging of cortical GABA dynamics in vivo. These results demonstrate that inhibitory signaling is dynamically structured across brain states and can be pharmacologically modulated. This tool offers new opportunities to explore the role of inhibition in health and disease at the mesoscale level.

neuroscience↗

bioRxiv2025

Branched and Linear F-actin Networks Control Directional Migration Switching Behavior on Aligned Collagen Fibrils

Directed cell migration is essential in many biological processes and is driven by a variety of directional cues, including aligned fibrils in the extracellular matrix (ECM), a phenomenon known as contact guidance. How different cells respond to aligned fibrils and how internal regulators like formins and Arp2/3 control contact guidance is unknown. In this study, a unique system to assemble aligned collagen fibrils on mica and to transfer them onto controllable substrates is used to probe contact guidance. This fibril alignment system reveals that cytoskeletal regulation through myosin contractility and not receptor expression drives contact guidance ability. Highly contractile cells exhibit high-fidelity contact guidance, weakly contractile cells ignore cues and moderately contractile cells use a mixture of both parallel and perpendicular migration strategies on aligned collagen fibrils. In addition to myosin contractility, formins and Arp2/3 control contact guidance in a reciprocal manner across a variety of cell types. Formins, mediators of linear F-actin structures, enhance contact guidance and Arp2/3, a mediator of branched F-actin structures, diminishes contact guidance. This controlled materials system reveals the importance of both myosin-mediated contractility as well as the antagonistic action of formins and Arp2/3 on contact guidance, providing potential targets to tune contact guidance.

bioengineering↗