Biology subjects

McAlinden, N.

Publications and source records attributed to McAlinden, N..

6 recordsLinked to original sources

bioRxiv2025

Depth-resolved fiber photometry of amyloid plaque signals in freely behaving Alzheimer's disease mice

Alzheimers disease pathology typically manifests itself across multiple brain regions yet assessment at this scale in mouse models remains a challenge. This hinders the development of novel therapeutic approaches. Here we introduce a novel fiber photometry approach to monitor amyloid pathology in freely behaving mice. We first demonstrated that flat fiber-based photometry can detect amyloid signals across multiple brain regions under anesthesia after injecting a blood-brain barrier permeable tracer, Methoxy-X04. The depth profile of in vivo fluorescent signals was correlated with postmortem histological plaque signals. After confirming its feasibility ex vivo, we chronically implanted a tapered fiber for depth-resolved fiber photometry in freely behaving mice. After injecting Methoxy-X04, fluorescent signals increased in a depth-specific manner in Alzheimers mice, but not in wild-type littermates. While fiber photometry has been widely adopted to monitor neuronal and non-neuronal activity, our approach expands the capabilities to monitor molecular pathologies such as amyloid plaques, even in a freely behaving condition.

neuroscience↗

bioRxiv2025

Chronically implantable μLED arrays for optogenetic cortical surface stimulation in mice

Cortical implants are a proven clinical neurotechnology with the potential to transform our understanding of cognitive processes. These processes rely on complex neuronal networks that are difficult to selectively probe or stimulate. Optogenetics offers cell-type specificity, but achieving the density and coverage required for chronic, high-resolution modulation remains a challenge. Here we present a 100-element {micro}LED array (200 {micro}m pixel pitch, 2 x 2 mm2 footprint) coupled into a miniaturised, flexible system suitable for chronic implantation and optogenetic stimulation of the surface of the mouse cortex. The {micro}LEDs can remain stable for over 300 hours continuous operation time in-vivo, allowing for months-long chronic experiments. Simultaneous electrophysiology recordings confirmed robust neuronal responses corresponding to low {micro}LED drive currents (<5 mA), minimising thermal effects and supporting future wireless operation. The spatial resolution of neuronal responses was consistent with a simulated model of light scattering in the cortical layers, enabling device optimisation. Behavioural experiments with chronically implanted mice demonstrated robust learning during discrimination tasks using spatially distinct optogenetic stimulation patterns.

neuroscience↗

bioRxiv2024

In vivo optogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity

Optogenetics allows manipulation of neural circuits in vivo with high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models). Here, we have developed, optimised, and tested in vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181 {micro}LEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies. Thinning the combined {micro}LED and needle backplane of the device from 300 {micro}m to 230 {micro}m improved the efficiency of light delivery to tissue by 80%, allowing lower {micro}LED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1{degrees}C. The device was tested in vivo in the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons. It was shown that the strongest optogenetic response occurred in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling - demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential (LFP) activity.

neuroscience↗

bioRxiv2022

An Optrode Array for Spatiotemporally Precise Large-Scale Optogenetic Stimulation of Deep Cortical Layers in Non-human Primates

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply in large brains, such as those of non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback projections. To address this unmet need, we have developed the Utah Optrode Array (UOA), a 10x10 glass needle waveguide array fabricated atop a novel opaque optical interposer then bonded to an electrically addressable LED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in monkey cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, simply by varying the number of activated LEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

neuroscience↗

bioRxiv2019

Simultaneous electrophysiological recording and fiber photometry in freely behaving mice

In vivo electrophysiology is the gold standard technique used to investigate sub-second neural dynamics in freely behaving animals. However, monitoring cell-type-specific population activity is not a trivial task. Over the last decade, fiber photometry based on genetically encoded calcium indicators has been widely adopted as a versatile tool to monitor cell-type-specific population activity in vivo. However, this approach suffers from low temporal resolution. Here, we combine these two approaches to monitor both sub-second field potentials and cell-type-specific population activity in freely behaving mice. By developing an economical custom-made system, and constructing a hybrid implant of an electrode and a fiber optic cannula, we simultaneously monitor artifact-free pontine field potentials and calcium transients in cholinergic neurons across the sleep-wake cycle. We find that pontine cholinergic activity co-occurs with sub-second pontine waves, called P-waves, during rapid eye movement sleep. Given the simplicity of our approach, simultaneous electrophysiological recording and cell-type-specific imaging provides a novel and valuable tool for interrogating state-dependent neural circuit dynamics in vivo.

neuroscience↗

bioRxiv2018

A multi-site MicroLED Optrode Array for Neural Interfacing

We present an electrically addressable optrode array capable of delivering light to 181 sites in the brain, each providing sufficient light to optogenetically excite hundreds of neurons in vivo, developed with the aim to allow behavioural studies in large mammals. The device is a glass microneedle array directly integrated with a custom fabricated microLED device, which delivers light to 100 needle tips and 81 interstitial surface sites, giving 2-level optogenetic excitation of neurons in vivo. Light delivery and thermal properties are evaluated, with the device capable of peak irradiances > 80 mW/mm2 per needle at 50 ms pulse widths with tissue temperature increase less than 1 {degrees}C. Future designs are explored through optical and thermal modelling and benchmarked against the current device.

neuroscience↗