Biology subjects

Kollo, M.

Publications and source records attributed to Kollo, M..

11 recordsLinked to original sources

bioRxiv2026

`Silent' mitral cells emerge from common feature subtraction

Whole-cell recordings from olfactory bulb mitral/tufted cells in awake mice revealed an inverse relationship between baseline activation and odour responses wherein cells that were spontaneously active tended to be inhibited by odours, while `silent' cells, quiet at baseline, tended to have vigorous odour responses. In this work we provide a normative explanation for these findings by extending previous sparse coding models of the olfactory system to include `common feature subtraction,' an odour-triggered variant of background subtraction in which the receptor contribution of features common to the odours being discriminated is subtracted. Using a circuit-level formulation of this computation consistent with the anatomy of the olfactory bulb we show how baseline activity cancels the effect of the common olfactory features on receptor activations, promoting inference of the target odours. We provide simulation results showing qualitative agreement with experimental findings. The model also predicts in closed form, without fitting, the slopes of the relationships between a cell's baseline and its common input and between its baseline and its odour response, and these predictions agree with simulations. Our model makes the experimentally testable prediction that a cell's baseline activation is not an intrinsic property, but reflects the negative of its recent activity.

neuroscience↗

bioRxiv2026

Decomposing representational drift across wake and sleep

Neural representations evolve over time, yet the relative contributions of online experience and offline states such as sleep remain unclear. Here, we recorded single-unit activity in the olfactory cortex of mice across cycles of awake odour exposure and sleep, and developed a low-rank decoder to track representational drift. We identified four orthogonal drift modes operating on distinct timescales, revealing that sleep and wake drive qualitatively different transformations, which indicates that offline reorganisation is not a simple continuation of online learning. Rather, sleep initiates an about-turn in the overall drift trajectory, which is uniquely characterised by a combination of decorrelation and rotation of odour representations. We also provide the first evidence for olfactory replay, occurring at ~2.5x temporal compression and associated with locally generated piriform cortex sharp waves. Together, these findings demonstrate that representational drift comprises state-dependent components, and reveal distinct contributions of wake and sleep to sensory representational change.

neuroscience↗

bioRxiv2025

A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain

Although topographical maps organize many peripheral sensory systems, it remains unclear whether olfactory sensory neurons (OSNs) choose which of the [~]1100 odor receptors (ORs) to express based upon their spatial location in the olfactory epithelium (OE) or instead ORs are scattered randomly. Here we reveal that each OR is expressed at a precise mean position along the OE dorsoventral axis, thereby instantiating a receptor map. This patterning reflects the differential use, by precursors and mature OSNs, of a coherent gene expression program controlled by a spatially-varying retinoic acid gradient; this program -- which includes key transcription factors and axon guidance genes -- translates position into a spatially appropriate distribution of OR choices and aligns the epithelial map of OR identity with the glomerular map present in the olfactory bulb. These results identify a transcriptional code that distinguishes and spatially organizes the vast array of sensory channels that comprise the olfactory system.

neuroscience↗

bioRxiv2025

Structure-Function Mapping of Olfactory Bulb Circuits with Synchrotron X-ray Nanotomography

Information is routed between brain areas via parallel streams. Neurons may share common inputs yet convey distinct information to different downstream targets. Here, we leverage the anatomical organisation of the mouse olfactory bulb (OB), where dozens of projection neurons (mitral and tufted cells, M/TCs) affiliate with a single input unit, a glomerulus1-3. To link functional properties of M/TCs to their anatomical glomerular association at scale, we combine in vivo two-photon (2P) imaging with synchrotron {micro}CT4-6 anatomical analysis and targeted X- ray nano-holotomography (XNH)7,8. Improving XNH resolution for mm3 volumes enables us to reliably identify subcellular features, automatically segment >80,000 cell nuclei in individual experiments, and delineate several hundred functionally imaged projection neurons and their detailed morphology, including up to 20 M/TCs per individual glomerulus ("sister" cells). In over 2400 sister cell pairs, we consistently find that odour response amplitudes to a panel of 47 monomolecular odours are conserved between sister cells, with, however, distinct responses to individual odours. Responses correlated with anatomical features such as cell body position and lateral dendritic arborisation. Thus, sister cells neither simply relay glomerular inputs nor are they dominated by network activity. Instead, they show a "balanced diversity" in their responses, enabling efficient encoding of odour stimuli whilst retaining the overall structure of odour space. Thus, synchrotron X-ray tomography can reliably link subcellular anatomy to function in a non-destructive way across the mm3 scale. With recent advances in X-ray optics9 and the emergence of 4th generation synchrotrons10,11, it becomes conceivable to extend this highly accessible approach to entire brain regions with increasing resolution.

neuroscience↗

bioRxiv2025

3D spatial transcriptomics reveals the molecular domain structure of the mouse olfactory bulb

A core organizing principle of the vertebrate brain is its symmetry along multiple axes. However, the precision with which neurons, circuit modules, and brain regions align to these axes remains poorly understood. Here, we used 3D spatial transcriptomics to reconstruct the anatomical and molecular organization of the mouse olfactory bulb. We mapped the positions of nearly one thousand molecularly distinct glomeruli, the structural and functional units of odor processing, revealing highly symmetric organization across hemispheres. Within each bulb, we delineated a curved axis of symmetry that divides pairs of sister glomeruli. Gene expression in the olfactory epithelium predicted glomerular position with near-glomerular resolution. However, glomerular symmetry did not extend to deeper layer mitral and granule cells, suggesting a reorganization from sensory input to cortical output pathways. Our findings provide the first comprehensive map of the olfactory bulb and reveal how its molecular structure is instructed by epithelial gene expression programs.

neuroscience↗

bioRxiv2023

An image segmentation method based on the spatial correlation coefficient of Local Moran's I

Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here we propose a spatial autocorrelation method based on Local Morans I coefficient to differentiate signal, background and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Morans method outperforms threshold-based method (TBM) in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the methods power in real situation we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage gated potassium channels. Morans method identified high intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Morans method is a rapid, simple image segmentation method optimal for variable and high nose conditions.

bioinformatics↗

bioRxiv2019

jULIEs: extracellular probes for recordings and stimulation in the structurally and functionally intact mouse brain

High signal-to-noise, scalable and minimally invasive recording and stimulation of the nervous system in intact animals is of fundamental importance to advance the understanding of brain function. Extracellular electrodes are among the most powerful tools capable of interfacing with large neuronal populations1-3. Neuronal tissue damage remains a major limiting factor in scaling electrode arrays, and has been found to correlate with electrode diameter across different electrode materials, such as microfabricated Michigan and Utah-style arrays4, MEMS and microsystems5, soft polymer or tungsten electrodes6 and Parylene C probes7. Small diameter ultramicroelectrodes (UMEs), while highly desirable, pose significant technical challenges such as reaching sufficient electrolyte-electrode coupling and limiting stray signal loss. To overcome these challenges, we have designed juxtacellular Ultra-Low Impedance Electrodes (jULIEs), a scalable technique for achieving high signal-to-noise electrical recordings as well as stimulation with UMEs. jULIEs are metal-glass composite UMEs thermally drawn to outer diameters (OD) of <25 {micro}m, with metal core diameters (ID) of as little as 1 {micro}m. We introduce a two-step electrochemical modification strategy that reduces UME coupling impedances by two orders of magnitude. Modifications enabled high signal-to-noise neural recordings in vivo through wires with micrometer scale core diameters. Histological and imaging experiments indicated that local vascular damage is minimal. Spikes reached amplitudes over 1 mV in vivo, indicating that recordings are possible in close proximity to intact neurons. Recording sites can be arranged in arbitrary patterns tailored to various neuroanatomical target structures and allowing parallel penetrations. jULIEs thus represent a versatile platform that allows for reliable recording and manipulation of neural activity in any areas of the functionally intact mammalian brain.

neuroscience↗

bioRxiv2019

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

Multi-channel electrical recordings of neural activity in the brain is an increasingly powerful method revealing new aspects of neural communication, computation, and prosthetics. However, while planar silicon-based CMOS devices in conventional electronics scale rapidly, neural interface devices have not kept pace. Here, we present a new strategy to interface silicon-based chips with three-dimensional microwire arrays, providing the link between rapidly-developing electronics and high density neural interfaces. The system consists of a bundle of microwires mated to large-scale microelectrode arrays, such as camera chips. This system has excellent recording performance, demonstrated via single unit and local-field potential recordings in isolated retina and in the motor cortex or striatum of awake moving mice. The modular design enables a variety of microwire types and sizes to be integrated with different types of pixel arrays, connecting the rapid progress of commercial multiplexing, digitisation and data acquisition hardware together with a three-dimensional neural interface.

neuroscience↗

bioRxiv2019

CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings

Mammalian brains consist of 10s of millions to 100s of billions of neurons operating at millisecond time scales, of which current recording techniques only capture a tiny fraction. Recording techniques capable of sampling neural activity at such temporal resolution have been difficult to scale: The most intensively studied mammalian neuronal networks, such as the neocortex, show layered architecture, where the optimal recording technology samples densely over large areas. However, the need for application-specific designs as well as the mismatch between the threedimensional architecture of the brain and largely two-dimensional microfabrication techniques profoundly limits both neurophysiological research and neural prosthetics.\n\nHere, we propose a novel strategy for scalable neuronal recording by combining bundles of glass-ensheathed microwires with large-scale amplifier arrays derived from commercial CMOS of in-vitro MEA systems or high-speed infrared cameras. High signal-to-noise ratio (<20 V RMS noise floor, SNR up to 25) is achieved due to the high conductivity of core metals in glass-ensheathed microwires allowing for ultrathin metal cores (down to <1 m) and negligible stray capacitance. Multi-step electrochemical modification of the tip enables ultra-low access impedance with minimal geometric area and largely independent of core diameter. We show that microwire size can be reduced to virtually eliminate damage to the blood-brain-barrier upon insertion and demonstrate that microwire arrays can stably record single unit activity.\n\nCombining microwire bundles and CMOS arrays allows for a highly scalable neuronal recording approach, linking the progress of electrical neuronal recording to the rapid scaling of silicon microfabrication. The modular design of the system allows for custom arrangement of recording sites. Our approach of employing bundles of minimally invasive, highly insulated and functionalized microwires to lift a 2-dimensional CMOS architecture into the 3rd dimension can be translated to other CMOS arrays such as electrical stimulation devices.

neuroscience↗

bioRxiv2017

Sniff-invariant intensity perception using olfactory bulb coding of inhalation dynamics

For stable perception of odor intensity, there must exist a neural correlate that is invariant across other parameters, such as the highly variable sniff cycle. Previous hypotheses suggest that variance in inhalation dynamics alters odor concentration profiles in the naris despite a constant environmental concentration. Using whole cell recordings in the olfactory bulb of awake mice, we directly demonstrate that increased sniffing frequency mimics the effect of odor concentration increase at the level of both mitral and tufted cell (MTC) firing rate responses and temporal responses. In contrast, we find that mice are capable of discriminating concentrations within short timescales despite highly variable sniffing behavior. We reason that the only way mice can differentiate a change in sniff parameters and a change in concentration is to encode information about the inhalation parameters in parallel. While conceivably this could be achieved via corollary discharge from respiration control centres, we find that the sniff-driven activity of MTCs without odor input is informative of the kind of inhalation that just occurred, allowing rapid detection of a change in inhalation. Thus, a possible reason for sniff modulation of the early olfactory system may be to inform downstream centres of nasal flow dynamics, so that an inference can be made about environmental concentration independent of sniff variance.

neuroscience↗

bioRxiv2017

Active sampling state dynamically enhances olfactory bulb odor representation

The olfactory bulb (OB) is the very first site of odor information processing, yet a wealth of contextual and learned information has been described in its activity. To investigate the mechanistic basis of contextual modulation, we use whole-cell recordings to measure odor responses across rapid (<30 min) learning episodes in identified mitral/tufted cells (MTCs). Across these learning episodes, we found that diverse response changes occur already during the first sniff cycle. Motivated mice develop active sniffing strategies across learning, and it is this change of active sampling state that dynamically modulates odor responses, resulting in enhanced discriminability and detectability of odor representation with learning. Evoking fast sniffing in different behavioral states demonstrates that response changes during active sampling exceed those predicted from purely feed-forward input. Finally, response changes are highly correlated in tufted cells, but not mitral cells, indicating cell-type specificity in the effect of active sampling, and resulting in increased odor detectability in the tufted and enhanced discriminability in the mitral cell population over the rapid learning episodes. Altogether, we show that active sampling state is a crucial component in modulating and enhancing olfactory bulb responsiveness on rapid timescales.

neuroscience↗