Biology subjects

Krumin, M.

Publications and source records attributed to Krumin, M..

8 recordsLinked to original sources

bioRxiv2026

High-throughput serial two-photon tomography with BakingTray and BrainSaw

Volumetric imaging is increasingly important in fields such as neuroscience, where quantifying structure and mapping features are inherently three-dimensional problems. Block-face serial two-photon tomography (STPT) has emerged as a powerful approach for high-resolution, whole-organ volumetric imaging. STPT avoids complex sample preparation and balances image quality, speed, and scalability. However, STPT remains niche, in part because of the absence of flexible, general-purpose control software. Here we present BakingTray, an open-source software platform for STPT that extends ScanImage. BakingTrays modular framework accommodates diverse hardware configurations and allows users to build systems customised to their needs. Twelve such systems, which we call BrainSaws, have been constructed worldwide since 2016, with more under construction, and have so far contributed to 35 research papers. The three systems at the Sainsbury Wellcome Centre alone have acquired over 7,000 samples in a busy multi-user facility. We demonstrate the platform across its core neuroscience applications: electrode track localisation, brain-wide cell counting, and bulk projection mapping. Beyond these, we map the cell-type-specific synaptic output of inhibitory neurons in the ventral lateral geniculate nucleus and, with whole-mount staining, amyloid plaques brain-wide in a mouse model of Alzheimers disease. BakingTray is a mature platform for groups or facilities needing a customised volumetric imaging solution, whether built new or converted cheaply from an existing two-photon microscope.

neuroscience↗

bioRxiv2025

Brainwide blood volume reflects opposing neural populations

The supply of blood to brain tissue is thought to depend on the overall neural activity in that tissue, and this dependence is thought to differ across brain regions and across brain states. Studies supporting these views, however, measured neural activity as a bulk quantity, and related it to blood supply following disparate events in different regions. Here we measure fluctuations in neuronal activity and blood volume across the mouse brain, and find that their relationship is consistent across brain states and brain regions but differs in two opposing brainwide neural populations. Functional Ultrasound Imaging (fUSI) revealed that whisking, a marker of arousal, is associated with brainwide fluctuations in blood volume. Simultaneous fUSI and Neuropixels recordings showed that neurons that increase vs. decrease activity with whisking have distinct hemodynamic response functions. Their summed contributions predicted blood volume across states. Brainwide Neuropixels recordings revealed that these two opposing populations coexist in the entire brain. Their differing contributions to blood volume largely explain the apparent differences in blood volume fluctuations across regions. The mouse brain thus contains two neural populations with opposite relation to brain state and distinct relationships to blood supply, which together account for brainwide fluctuations in blood volume.

neuroscience↗

bioRxiv2025

Suite3D: Volumetric cell detection for two-photon microscopy

In two-photon imaging of neuronal activity it is increasingly common to acquire 3-dimensional volumes. However, these volumes are typically processed plane by plane, leading to uncorrected axial movement, duplicated cells across planes, reduced signal-to-noise ratio per cell, and missed cells. To overcome these limitations, we introduce Suite3D, a volumetric cell detection pipeline. Suite3D corrects for rigid and non-rigid 3D brain motion, both lateral and axial. It detects neurons using 3D correlation, improving detectability. Finally, it performs 3D segmentation, identifying cells across imaging planes. We validated Suite3D with data from conventional multi-plane microscopes and advanced volumetric microscopes, at multiple resolutions and in multiple brain regions, and with ground truth anatomical labelling. Suite3D successfully detected cells appearing on multiple imaging planes, improving cell detectability and signal quality, avoiding duplications, and running faster than a prior volumetric pipeline. Suite3D offers a powerful solution for analyzing volumetric two-photon data.

neuroscience↗

bioRxiv2025

Neuropixels Opto: Combining high-resolution electrophysiology and optogenetics

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations, and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70 m wide, 1 cm long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent an unprecedented tool for recording, identifying, and manipulating neuronal populations.

neuroscience↗

bioRxiv2021

Neural basis of functional ultrasound signals

Functional ultrasound imaging (fUSI) is a popular method for measuring blood flow and thus infer brain activity, but it relies on the physiology of neurovascular coupling and requires extensive signal processing. To establish to what degree its trial-by-trial signals reflect neural activity, we performed simultaneous fUSI and neural recordings with Neuropixels probes in awake mice. fUSI signals strongly correlated with the slow (<0.3 Hz) fluctuations in local firing rate, and were closely predicted by the smoothed firing rate of local neurons, particularly putative inhibitory neurons. The optimal smoothing filter had width ~3 s, matched the hemodynamic response function of awake mouse, was invariant across mice and stimulus conditions, and similar in cortex and hippocampus. fUSI signals also matched neural firing spatially: firing rates were as highly correlated across hemispheres as fUSI signals. Thus, hemodynamic signals measured by ultrasound bear a simple and accurate relationship to neuronal firing.

neuroscience↗

bioRxiv2020

Task specificity in mouse parietal cortex

Parietal cortex is implicated in a variety of behavioral processes, but it is unknown whether and how individual neurons participate in multiple tasks. We trained head-fixed mice to perform two visual decision tasks involving a steering wheel or a virtual T-maze, and recorded from the same parietal neurons during the two. Neurons that were active during the T-maze task were typically inactive during the steering-wheel task, and vice versa. Recording from the same neurons in the same apparatus without task stimuli yielded the same specificity as in the task, suggesting that task specificity depends on physical context. To confirm this, we trained some mice in a third task combining the steering wheel with the visual environment of the T-maze. This hybrid task engaged the same neurons as the steering-wheel task. Thus, participation by neurons in mouse parietal cortex is task-specific, and this specificity is determined by physical context.

neuroscience↗

bioRxiv2019

Retinal outputs depend on behavioural state

The operating mode of the visual system depends on behavioural states such as arousal1,2. This dependence is seen both in primary visual cortex3-7 (V1) and in subcortical brain structures receiving direct retinal input4,8. Here we show that this effect arises as early as in the output of the retina. We first measured activity in a region that receives retinal projections9, the superficial superior colliculus (sSC), and found that this activity strongly depended on behavioural state. This modulation was not mediated by feedback inputs from V1 as it was immune to V1 inactivation. We then used Neuropixels probes10 to record activity in the optic tract, and we found some retinal axons whose activity significantly varied with arousal, even in darkness. To characterize these effects on a larger sample of retinal outputs, we imaged the activity of retinal boutons11,12 in sSC during behaviour using a calcium indicator. The activity of these boutons correlated with arousal as strongly as that of sSC neurons, and this correlation persisted also during darkness. These results reveal a novel property of retinal function in mice, which could be observed only during behaviour: retinal outputs are modulated by behavioural state before they reach the rest of the brain.

neuroscience↗

bioRxiv2017

Decision and navigation in mouse parietal cortex

Posterior parietal cortex (PPC) has been implicated in navigation, in the control of body movement, and in visually-guided decisions. Seeking to relate these views, we measured activity in populations of PPC neurons while mice performed a virtual navigation task driven by visual decisions. We found that PPC neurons are selective for specific combinations of the animals spatial position and heading angle. This selectivity closely predicted both the activity of individual PPC neurons, and the arrangement of their collective firing patterns in choice-selective sequences. These sequences reflected the influence on PPC of the animals navigation trajectory. An alternative model in which PPC activity encoded position and decision performed more poorly, and a model with all three variables barely outperformed the simple position-heading model. Alternative models based on visual or motor variables were inferior. We conclude that when mice use vision to choose their trajectories, a large fraction of parietal cortex activity can be predicted from simple attributes such as spatial position and heading.

neuroscience↗