Biology subjects

Kerr, J. N.

Publications and source records attributed to Kerr, J. N..

5 recordsLinked to original sources

bioRxiv2025

Simultaneous 2- and 3-photon multiplane imaging across cortical layers in freely moving mice

Head-mounted multiphoton microscopes enable imaging of activity from neuronal populations spread throughout the cortical layers in freely moving mice, but so far have been restricted to recording from one cortical layer at a time. Here, combining 2- and 3-photon based excitation delivered through multiple fibers, we built a head-mounted multiplane microscope enabling near simultaneous imaging (8ns between planes) of neuronal activity from five vertically separated planes, spread across multiple cortical layers. Both excitation pathways had remote focusing mechanisms for fine axial adjustments enabling activity recordings from the same neuronal populations over weeks in freely behaving mice. The lightweight microscope utilized an onboard, 2-channel detection system designed to enable activity recordings from neuronal populations spread across visual-cortex layers in both lit and dark conditions as well as imaging activity across posterior parietal cortex layers during complex gap-crossing behaviors. We show that during gap- crossing tasks, layer 5 and 2/3 neuronal subpopulations in posterior parietal cortex have differential pattern sequences during free decision making. Editorial summaryA light-weight head-mounted multiplane microscope allows simultaneous imaging from >1800 neurons spread across the cortical layers in freely moving mice performing complex behavioral tasks, sampled over weeks.

neuroscience↗

bioRxiv2024

Sustained ON alpha retinal ganglion cells in the temporal retina exhibit task-specific regional adaptions in dendritic signal integration

Various retinal ganglion cells (RGCs) show regional adaptations, for instance, to increase visual acuity. However, for many RGC types, it is not known how they vary in their signalprocessing properties across the retina. In the mouse retina, sustained ON alpha (sON) RGCs were found to have differences in morphology and receptive field sizes along the nasotemporal axis, and temporal sON RGCs are likely to play a role in visually guided hunting. Thus, we hypothesised that this cell type also exhibits regional adaptations on the level of dendritic signal processing and that these adaptations are advantageous for prey capture. Here, we measured dendritic signals from individual sON RGCs at different locations in the exvivo whole-mount mouse retina using two-photon microscopy. We measured both postsynaptic Ca2+ signals at the dendrites of individual RGCs and presynaptic glutamate signals from bipolar cells (BCs). We found that temporal sON RGC dendrites exhibit, in addition to the expected sustained-ON signals with only weak surrounds, signals with strong surround suppression, which were not present in nasal sON RGCs. This difference was also present in the excitatory presynaptic inputs from BCs, suggesting a presynaptic origin. Finally, using population models in an encoder-decoder paradigm, we showed that these adaptations might be beneficial for detecting crickets in hunting behaviour.

neuroscience↗

bioRxiv2022

A three-photon head-mounted microscope for imaging all layers of visual cortex in freely moving mice.

Recent advances in head-mounted microscopes have enabled imaging of neuronal activity using genetic-tools in freely moving mice but these microscopes are restricted to recording in minimally lit arenas and imaging upper cortical layers. Here we built a 2 gram, three-photon excitation-based microscope, containing a z-drive that enabled access to all cortical layers while mice freely behaved in a fully lit environment. We show that neuronal population activity in cortical layer-4 and layer-6 was differentially modulated by lit and dark conditions during free exploration.

neuroscience↗

bioRxiv2021

Anatomically-based skeleton kinetics and pose estimation in freely-moving rodents

Forming a complete picture of the relationship between neural activity and body kinetics requires quantification of skeletal joint biomechanics during behavior. However, without detailed knowledge of the underlying skeletal motion, inferring joint kinetics from surface tracking approaches is difficult, especially for animals where the relationship between surface anatomy and skeleton changes during motion. Here we developed a videography-based method enabling detailed three-dimensional kinetic quantification of an anatomically defined skeleton in untethered freely-behaving animals. This skeleton-based model has been constrained by anatomical principles and joint motion limits and provided skeletal pose estimates for a range of rodent sizes, even when limbs were occluded. Model-inferred joint kinetics for both gait and gap-crossing behaviors were verified by direct measurement of limb placement, showing that complex decision-making behaviors can be accurately reconstructed at the level of skeletal kinetics using our anatomically constrained model.

neuroscience↗

bioRxiv2018

Accurate action potential inference from a calcium sensor protein through biophysical modeling

Multiphoton imaging of genetically encoded calcium indicators is routinely used to report activity from populations of spatially resolved neurons in vivo. However, since the relationship between fluorescence and action potentials (APs) is nonlinear and varies over neurons, quantitatively inferring AP discharge is problematic. To address this we developed a biophysical model of calcium binding kinetics for the indicator GCaMP6s that accurately describes AP-evoked fluorescence changes in vivo. The models physical interpretation allowed the same parameters to describe GCaMP6s binding kinetics for both in vitro binding assays and in vivo imaging. Using this model, we developed an algorithm to infer APs from fluorescence and measured its accuracy with cell-attached electrical recordings. This approach consistently inferred more accurate AP counts and times than alternative methods for firing rates from 0 to >20 Hz, while requiring less training data. These results demonstrate the utility of quantitative, biophysically grounded models for complex biological data.

neuroscience↗