Biology subjects

Go, M. A.

Publications and source records attributed to Go, M. A..

5 recordsLinked to original sources

bioRxiv2025

Longitudinal three-photon imaging for tracking amyloid plaques and vascular degeneration in a mouse model of Alzheimer's disease

SignificanceVascular abnormalities may contribute to amyloid-beta accumulation and neurotoxicity in Alzheimers disease (AD). Monitoring vascular degeneration as AD progresses is essential. Three-photon fluorescence microscopy (3PM) enables high-resolution deep tissue imaging with minimal invasiveness and photodamage. AimThis proof-of-concept study established a longitudinal 3P imaging pipeline to quantify vascular and amyloid plaque changes in the APPNL-G-F mouse model. ApproachA cranial window allowed repeated 3P imaging at four-week intervals beginning at five weeks after surgery. Vessels labelled with Texas-Red were segmented using DeepVess, while plaques labelled with methoxy-XO4 were segmented using custom scripts. Quantitative analyses assessed vascular parameters (diameter, tortuosity, length, inter-vessel distance, total volume) and plaque metrics (radius, total volume). ResultsWe imaged the same field over 4 weeks quantifying an overall decrease in vasculature and increase in amyloid plaques between two sessions. Significant changes in vessel diameter, inter-vessel distance, as well as alterations in vessel length and plaques radius were observed. Changes in vessel tortuosity were not significant. ConclusionsWe demonstrate the potential of three-photon imaging to track vascular and amyloid-related changes in deep cortical structures. It offers a tool for studying the interplay between vascular and amyloid pathologies in AD, supporting future research into disease mechanisms and therapeutic strategies.

neuroscience↗

bioRxiv2025

Amyloid pathology reduces dynamic range and disrupts neural coding in a mouse model of Alzheimer's Disease

Alzheimers disease (AD) disrupts neural circuits vital for memory and cognition. Using two-photon calcium imaging in behaving 5xFAD mice, we examined how amyloid pathology alters hippocampal CA1 activity and spatial coding. We found elevated baseline activity but reduced locomotion-driven firing, leading to a diminished neuronal dynamic range. To our knowledge, this is the first direct experimental evidence for reduced dynamic range in an AD model. These abnormalities were strongest near amyloid plaques and became more widespread with age. We also observed altered network synchrony, degraded spatial coding and increased neuronal response variability. Furthermore, place fields emerged more slowly in both familiar and novel environments, indicating impaired recall and learning. By showing a link between local plaque pathology and impaired flexible modulation of CA1 activity and progressive deficits in spatial memory coding, our study offers new insights into the circuit basis of cognitive decline in AD.

neuroscience↗

bioRxiv2025

Disrupted spatial and contextual memory encoding in the hippocampus of 5xFAD mice precedes cognitive impairment

Alzheimers disease (AD) is characterized by progressive memory decline, yet how hippocampal representations change at early AD stages remains largely unknown. In this study, we utilized a real-world head-fixed spatial alternation task combined with in vivo two-photon imaging to investigate hippocampal CA1 representations in 5xFAD mice. While 7-9 month old 5xFAD mice showed significant deficits in task learning, 2-4 month old mice performed normally, enabling assessment of hippocampal coding prior to behavioral decline. At this early stage, CA1 neurons exhibited intact global spatial encoding but demonstrated impaired task-related place cell representations. Contextual representations revealed by trajectory-dependent coding were weakened at both the population and single cell levels, accompanied by a notable shift from predominantly retrospective to more prospective encoding during behavioral choices. During task learning, longitudinally unstable place cells showed greater impairments in spatial coding, whereas stable place cells remained largely preserved in early-stage AD mice. Additionally, chemogenetic activation of basal forebrain cholinergic neurons increased spatial information and within-session stability, while promoting trajectory-dependent coding in these early-stage 5xFAD mice. Together, these findings reveal selective early impairments in hippocampal task-related spatial and contextual representations in AD that precede overt deficits in spatial alternation performance and remains amenable to cholinergic modulation.

neuroscience↗

bioRxiv2020

Place cells in head-fixed mice navigating a floating real-world environment

The hippocampal place cell system in rodents has provided a major paradigm for the scientific investigation of memory function and dysfunction. Place cells have been observed in area CA1 of the hippocampus of both freely moving animals, and of head-fixed animals navigating in virtual reality environments. However, spatial coding in virtual reality preparations has been observed to be impaired. Here we show that the use of a real-world environment system for head-fixed mice, consisting of a track floating on air, provides some advantages over virtual reality systems for the study of spatial memory. We imaged the hippocampus of head-fixed mice injected with the genetically encoded calcium indicator GCaMP6s while they navigated circularly constrained or open environments on the floating platform. We observed consistent place tuning in a substantial fraction of cells with place fields remapping when animals entered a different environment. When animals re-entered the same environment, place fields typically remapped over a time period of multiple days, faster than in freely moving preparations, but comparable with virtual reality. Spatial information rates were within the range observed in freely moving mice. Manifold analysis indicated that spatial information could be extracted from a low-dimensional subspace of the neural population dynamics. This is the first demonstration of place cells in head-fixed mice navigating on an air-lifted real-world platform, validating its use for the study of brain circuits involved in memory and affected by neurodegenerative disorders.

neuroscience↗

bioRxiv2017

Multiphoton minimal inertia scanning for fast acquisition of neural activity signals

Multi-photon laser scanning microscopy provides a powerful tool for monitoring the spatiotemporal dynamics of neural circuit activity. It is, however, intrinsically a point scanning technique. Standard raster scanning enables imaging at subcellular resolution; however, acquisition rates are limited by the size of the field of view to be scanned. Recently developed scanning strategies such as Travelling Salesman Scanning (TSS) have been developed to maximize cellular sampling rate by scanning only regions of interest in the field of view corresponding to locations of interest such as somata. However, such strategies are not optimized for the mechanical properties of galvanometric scanners. We describe here the Adaptive Spiral Scanning (SSA) algorithm, which fits a set of near-circular trajectories to the cellular distribution to avoid inertial drifts of galvanometer position. We compare its performance to raster scanning and TSS in terms of cellular sampling frequency and signal-to-noise ratio (SNR). Using surrogate neuron spatial position data, we show that SSA acquisition rates are an order of magnitude higher than those for raster scanning and generally exceed those achieved by TSS for neural densities comparable with those found in the cortex. We show that this result also holds true for in vitro hippocampal mouse brain slices bath loaded with the synthetic calcium dye Cal-520 AM. The ability of TSS to \"park\" the laser on each neuron along the scanning trajectory, however, enables higher SNR than SSA when all targets are precisely scanned. Raster scanning has the highest SNR but at a substantial cost in number of cells scanned. To understand the impact of sampling rate and SNR on functional calcium imaging, we used the Cramer-Rao Bound on evoked calcium traces recorded simultaneously with electrophysiology traces to calculate the lower bound estimate of the spike timing occurrence. The results show that TSS and SSA achieve comparable accuracy in spike time estimates compared to raster scanning despite their lower SNR. SSA is an easily implementable way for standard multi-photon laser scanning systems to gain temporal precision in the detection of action potentials while scanning hundreds of active cells.

neuroscience↗