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Henschke, J. U.

Publications and source records attributed to Henschke, J. U..

3 recordsLinked to original sources

A uniform tissue-clearing framework and mesoSPIM-ultra enable cm-scale single-neuron tracing

Tissue-clearing and light-sheet microscopy have transformed volumetric imaging of intact organs, yet limited mechanistic understanding of dehydration-based clearing continues to constrain rational protocol design and broader applicability. Here, we define the cardinal chemical and physical principles underlying dehydration-based tissue-clearing and establish a new pipeline for large-volume imaging. To maximize imaging performance, we developed the "mesoSPIM-ultra", an upgraded mesoSPIM platform with a temperature-controlled sample chamber, a large field-of-view (FoV) camera and specialized optics to achieve long-working-distance, high-resolution imaging of cleared samples. We applied this approach to investigate the projectome of Chx10+ neurons, a cell population with complex axonal morphologies along the entire mouse spinal-cord and brain, and implicated in ipsilateral orienting behaviors. By combining behavioral analysis with post-hoc single-neuron reconstructions, we revealed previously inaccessible branching architectures and long-range projections extending from the brainstem to the spinal cord. Together, our work establishes a mechanistic foundation for tissue-clearing and scalable imaging.

neuroscience↗

Neural networks representing temporal expectation in mice

The ability to attend to specific moments in time is crucial for survival across species facilitating perception and motor performance by leveraging prior temporal knowledge for predictive processing. Despite its importance, the neural mechanisms underlying the utilization of macro-scale and meso-scale neural resources during temporal processing and their relationship to behavioural strategies and motor responses remain largely unexplored. To investigate the capacity for predictive temporal structure of multisensory stimuli to optimize motor behaviour, we established a behavioural paradigm, in which mice were trained to an auditory-cue and visual-target presented at expected or unexpected temporal delays. Using a combination of stimulus-evoked and resting-state functional magnetic resonance imaging, we examined task-related evoked activity in brain-wide networks and found that that the formation of temporal expectations relying on accumulated sensory information and combined multisensory input involves plasticity across large macro-scale cortical networks comprised of primary sensory systems, sensory association areas including posterior parietal cortex, retrosplenial cortex, prefrontal top-down executive control centres of the brain, as well as hippocampal networks. Additionally, employing in vivo two-photon calcium imaging, we explored local single-cell dynamics within the posterior parietal cortex during this task and found that temporal expectation could be decoded directly from neuronal activity within this brain region. Overall, our study provides insights into the neural correlates underlying the formation of multisensory temporal expectations in the mouse brain and highlights the recruitment of neural resources across temporally-driven statistical learning processes.

neuroscience↗

A layer-specific model of cortical sensory aging

The segregation of processes into cortical layers is a convergent feature in animal evolution. However, how changes in the cortical layer architecture interact with sensory system function and dysfunction remains unclear. We conducted functional and structural layer-specific in-vivo 7T-MRI of the primary somatosensory cortex in two cohorts of healthy younger and older adults. Input layer IV is enlarged and more myelinated in older adults, and associated with extended sensory input signals. Age-related cortical thinning is driven by deep layers and accompanied by increased myelination, but there is no clear evidence for reduced inhibition. Calcium imaging and histology in younger and older mice reveal increased sensory-evoked neuronal activity accompanied by increased parvalbumin expression as a potential inhibitory balance, with dynamic changes in layer-specific myelination across age groups. Using multimodal imaging, we demonstrate that middle and deep layers show specific sensitivity to aging across species.

neuroscience↗