The integration of synaptic inputs is a fundamental function of neurons. In the traditional model, excitatory inputs are summed at the soma to generate action potentials. However, how synaptic inputs are integrated by dendrites in vivo remains poorly explored. We used intravital two-photon dendritic imaging with a genetically encoded voltage indicator (accelerated sensor of action potentials 5) together with somatic whole-cell patch clamp recordings to investigate how synaptic depolarizations are transferred to the soma in pyramidal neurons of the mouse somatosensory cortex. We studied the integration of synaptic inputs under spontaneous and sensory-evoked conditions, as well as following electrical and optogenetic stimulation. In all cases, while multiple inputs evoked measurable depolarizations in the cell body, isolated synaptic potentials were strongly attenuated. Our results suggest that isolated synaptic inputs have a minimal contribution to somatic depolarization, whereas coincident inputs within short temporal windows are more effective, indicating a regime of dendritic integration that favors coincident or clustered neuronal activity in cortical networks.

Neurons interact in networks distributed throughout the brain. While much effort has focused on whole-brain calcium imaging, advances in genetically encoded voltage indicators raise the question of whether it might be possible to image neuronal voltage across entire brains. Achieving this requires a microscope with high volumetric imaging rates and signal-to-noise ratio. Here we present a remote-scanning light-sheet microscope capable of imaging genetically encoded voltage indicator-expressing neurons distributed throughout much of the brain of larval zebrafish at a volumetric rate of 200.8 Hz. We measured voltage traces from approximately one-quarter of all brain neurons. We found that neurons firing at different times during a sequence occupied different locations: visually evoked sequences mapped across the optic tectum, whereas stimulus-independent bursts were mapped across the cerebellum and medulla. Imaging voltage of neurons distributed in many brain regions may open new frontiers for understanding fundamental neural system operations.

Sub-millivolt membrane potential (V) dynamics in multicellular non-excitable networks have remained largely inaccessible due to insufficiently sensitive imaging tools. Here, we introduce rEstus2s, a next-generation genetically encoded voltage indicator that overcomes this barrier by enabling high-resolution V imaging. Using rEstus2s, we uncover bioelectric contact inhibition (BCI), a biophysical principle in which gap junction coupling passively stabilizes V by suppressing electrical volatility. We show that V variance scales inversely with network size (1/n), reflecting a transition from stochastic single-cell behavior to collective electrical stability. Ca²⁺-activated oncogenic ion channels, including ANO1 and K3.1, drive pronounced electrical volatility in isolated cells, but BCI effectively attenuates this volatility in electrically coupled networks. Disruption of gap junction coupling abolishes BCI and restores high electrical volatility. These findings establish a unifying framework for how multicellular systems maintain electrical homeostasis and reveal gap junction coupling as a key determinant of bioelectric stability in health and disease.

Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.

Neurons interact in networks distributed throughout the brain. While much effort has focused on whole-brain calcium imaging, advances in genetically encoded voltage indicators raise the question of whether it might be possible to image neuronal voltage across entire brains. Achieving this requires a microscope with high volumetric imaging rates and signal-to-noise ratio. Here we present a remote-scanning light-sheet microscope capable of imaging genetically encoded voltage indicator-expressing neurons distributed throughout much of the brain of larval zebrafish at a volumetric rate of 200.8 Hz. We measured voltage traces from approximately one-quarter of all brain neurons. We found that neurons firing at different times during a sequence occupied different locations: visually evoked sequences mapped across the optic tectum, whereas stimulus-independent bursts were mapped across the cerebellum and medulla. Imaging voltage of neurons distributed in many brain regions may open new frontiers for understanding fundamental neural system operations.

Hemorrhagic shock remains a leading cause of mortality due to impaired oxygen delivery following severe blood loss. Hemoglobin-based oxygen carriers (HBOCs) are promising alternatives to red blood cell transfusion; however, their molecular size critically governs nitric oxide (NO) scavenging, vascular reactivity, and overall safety. Here, we systematically evaluated acellular human hemoglobin (hHb) and four polymerized hemoglobin formulations with progressively increasing molecular weights (PolyhHb-10, ∼1080 kDa; PolyhHb-12, ∼1200 kDa; PolyhHb-15, ∼1490 kDa; and PolyhHb-16, ∼1570 kDa) to define size-dependent determinants of vascular function. Ex vivo, isolated mesenteric arterioles from New Zealand white rabbits were perfused with HBOC-whole blood mixtures (1:0, 1:1, and 1:3) across physiologically relevant flow rates to quantify shear-mediated vasodilation and endothelial function. The acetylcholine challenge was used to probe NO bioavailability. In vivo validation was performed in Golden Syrian hamsters using a dorsal window chamber model to assess microvascular hemodynamics, including the vessel diameter, blood flow, and functional capillary density. PolyhHb-12 consistently preserved endothelial-dependent vasodilation and exhibited minimal NO scavenging across conditions. In contrast, larger polymers (PolyhHb-15 and PolyhHb-16) showed paradoxically increased NO scavenging despite improved capillary perfusion, indicating a trade-off between microcirculatory flow enhancement and endothelial signaling. In vivo, increasing the molecular size yielded diminishing returns in overall hemodynamic stability. Together, these findings identify an intermediate molecular size as optimal for balancing rheological properties, NO bioavailability, and vascular function. PolyhHb-12 emerges as a lead candidate, supporting the design of next-generation HBOCs with improved safety and efficacy for hemorrhagic shock resuscitation.