Biology subjects

Ackels, T.

Publications and source records attributed to Ackels, T..

8 recordsLinked to original sources

bioRxiv2026

Decorrelation by gain control in the mouse olfactory bulb

Classifying sensory stimuli requires neural circuits to transform overlapping inputs into representations that are more distinct and decodable. Odour representations in the olfactory bulb (OB) have been reported to decorrelate from sensory input to output, a transformation thought to enhance odour separability. What has been missing is a systematic quantification of this transformation across odours, and a mechanistic account of how it can be implemented by OB circuitry. Using in vivo two-photon calcium imaging, we recorded glomerular input and output responses to a chemically diverse panel of 47 odours in mice. We observed a robust decorrelation of odour-evoked activity patterns from input to output: correlations between odour representations were consistently reduced, while overall response variance was preserved. This transformation increased the dimensionality of the population code and improved the separability of odour representations. Consistent with this, classification analyses showed that odour identity could be decoded with significantly higher accuracy at the output. To understand the mechanisms underlying this transformation, we developed a linear model of the OB with different levels of connectivity. Models in which each channel underwent only self-gain modulation reproduced the observed decorrelation nearly as well as models with fully unconstrained lateral connectivity. Analysis revealed that channels contributing unique information were selectively amplified, while redundant channels were attenuated. Together, our results show that the OB implements a measurable input-output transformation that enhances odour separability. By combining systematic recordings with computational modelling, we found that feedforward gain modulation serves as a simple and scalable mechanism capable of explaining the observed decorrelation, reframing how we understand the functional architecture of early olfactory processing.

neuroscience↗

bioRxiv2025

Mice discriminate odour source distance via sub-sniff temporal features of odour plumes

Rodents rely on olfaction to navigate complex environments, particularly where visual cues are limited. Yet how they estimate the distance to an odour source remains unclear. The spatiotemporal dynamics of natural odour plumes, shaped by airflow turbulence, offer valuable cues for locating odour sources. Here, we show that mice can discriminate odour sources placed at different distances by extracting information from the sub-sniff temporal structure of naturalistic odour plumes. Using a wind tunnel and an olfactory virtual reality system, we generated dynamic plumes and demonstrated, through high-throughput automated behaviour, that mice distinguish near from far sources based on odour fluctuations operating faster than their respiratory cycle. Two-photon calcium imaging of olfactory bulb projection neurons revealed that distance-dependent responses are present in a small subset of mitral and tufted cells, and that population activity encodes source distance. Critically, neural responses correlated more strongly with high-frequency plume features than with mean odour concentration. Our results identify a neural basis for distance estimation from odour dynamics and highlight the importance of rapid temporal processing in mammalian olfaction.

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↗

bioRxiv2022

Sample preparation and warping accuracy for correlative multimodal imaging in the mouse olfactory bulb using 2-photon, synchrotron X-ray and volume electron microscopy

Integrating physiology with structural insights of the same neuronal circuit provides a unique approach to understanding how the mammalian brain computes information. However, combining the techniques that provide both streams of data represents an experimental challenge. When studying glomerular column circuits in the mouse olfactory bulb, this approach involves e.g. recording the neuronal activity with in vivo 2-photon (2P) calcium imaging, retrieving the circuit structure with synchrotron X-ray computed tomography with propagation-based phase contrast (SXRT) and/or serial block-face electron microscopy (SBEM) and correlating these datasets. Sample preparation and dataset correlation are two key bottlenecks in this correlative workflow. Here, we first quantify the occurrence of different artefacts when staining tissue slices with heavy metals to generate X-ray or electron contrast. We report improvements in the staining procedure, ultimately achieving perfect staining in [~]67% of the 0.6 mm thick olfactory bulb slices that were previously imaged in vivo with 2P. Secondly, we characterise the accuracy of the spatial correlation between functional and structural datasets. We demonstrate that direct, single-cell precise correlation between in vivo 2P and SXRT tissue volumes is possible and as reliable as correlating between 2P and SBEM. Altogether, these results pave the way for experiments that require retrieving physiology, circuit structure and synaptic signatures in targeted regions. These correlative function-structure studies will bring a more complete understanding of mammalian olfactory processing across length scales and time.

neuroscience↗

bioRxiv2021

Functional and multiscale 3D structural investigation of brain tissue through correlative in vivo physiology, synchrotron micro-tomography and volume electron microscopy

Attributing in vivo neurophysiology to the brains ultrastructure requires a large field of view containing contextual anatomy. Electron microscopy (EM) is the gold standard technique to identify ultrastructure, yet acquiring volumes containing full mammalian neural circuits is challenging and time consuming using EM. Here, we show that synchrotron X-ray computed tomography (SXRT) provides rapid imaging of EM-prepared tissue volumes of several cubic millimetres. Resolution was sufficient for distinguishing cell bodies as well as for tracing apical dendrites in olfactory bulb and hippocampus, for up to 350 m. Correlating EM with SXRT allowed us to associate dendritic spines on pyramidal cell apical dendrites in the stratum radiatum to their corresponding soma locations. Superficial pyramidal neurons had larger spine apparatus density compared to deeper ones, implying differential synaptic plasticity for superficial and deeper cells. Finally, we show that X-ray tomography and volume EM can be reliably correlated to prior in vivo imaging. Thus, combining functional measurements with multiscale X-ray microscopy and volume EM establishes a correlative workflow that enables functional and structural investigation of subcellular features in the context of cellular morphologies, tissues and ultimately whole organs.

neuroscience↗

bioRxiv2020

Molecular characterization of projection neuron subtypes in the mouse olfactory bulb

Projection neurons (PNs) in the mammalian olfactory bulb (OB) receive direct input from the nose and project to diverse cortical and subcortical areas. Morphological and physiological studies have highlighted functional heterogeneity, yet no molecular markers have been described that delineate PN subtypes. Here, we used viral injections into olfactory cortex and fluorescent nucleus sorting to enrich PNs for high-throughput single nucleus and bulk RNA deep sequencing. Transcriptome analysis and RNA in situ hybridization identified three mitral and five tufted cell populations with characteristic transcription factor network topology and cell adhesion and excitability-related gene expression. Finally, by integrating bulk and snRNA-seq data we propose that different mitral cell populations selectively project to different regions of olfactory cortex. Together, we have identified potential molecular and gene regulatory mechanisms underlying PN diversity and provide new molecular entry points into studying the diverse functional roles of mitral and tufted cell subtypes.

neuroscience↗

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

Mammalian olfaction is a high temporal bandwidth sense

Odours are transported in turbulent plumes resulting locally in highly fluctuating odour concentration (Celani et al., 2014; Murlis et al., 1992; Mylne and Mason, 1991; Shraiman and Siggia, 2000). Yet, whether mammals can make use of the ensuing temporal structure (Celani et al., 2014; Crimaldi and Koseff, 2001; Murlis et al., 1992; Mylne and Mason, 1991; Schmuker et al., 2016; Vickers, 2000) to extract information about the olfactory environment remains unknown. Here, we use dual-energy photoionisation recording with >300 Hz bandwidth to simultaneously determine odour concentrations of two odours in air. We show that temporal correlation of odour concentrations reliably predicts whether odorants emerge from the same or different sources in normal turbulent environments outside and in laboratory conditions. To replicate natural odour dynamics in a reproducible manner we developed a multichannel odour delivery device allowing presentation of several odours with 10 ms temporal resolution. Integrating this device in an automated operant conditioning system we demonstrate that mice can reliably discriminate the correlation structure of odours at frequencies of up to 40 Hz. Consistent with this finding, output neurons in the olfactory bulb show segregated responses depending on the correlation of odour stimuli with populations of 10s of neurons sufficient to reach behavioural performance. Our work thus demonstrates that mammals can perceive temporal structure in odour stimuli at surprisingly fast timescales. This in turn might be useful for key behavioural challenges (Jacobs, 2012) such as odour source separation (Hopfield, 1991), figure-ground separation (Rokni et al., 2014) or odour localisation (Vergassola et al., 2007; Vickers, 2000).

neuroscience↗