Biology subjects

Mochizuki, C.

Publications and source records attributed to Mochizuki, C..

6 recordsLinked to original sources

bioRxiv2025

Map of spiking activity underlying change detection in the mouse visual system

Visual behavior requires coordinated activity across hierarchically organized brain circuits. Understanding this complexity demands datasets that are both large-scale (sampling many areas) and dense (recording many neurons in each area). Here we present a database of spiking activity across the mouse visual system--including thalamus, cortex, and midbrain--while mice perform an image change detection task. Using Neuropixels probes, we record from >75,000 high-quality units in 54 mice, mapping area-, cortical layer-, and cell type-specific coding of sensory and motor information. Modulation by task-engagement increased across the thalamocortical hierarchy but was strongest in the midbrain. Novel images modulated cortical (but not thalamic) responses through delayed recurrent activity. Population decoding and optogenetics identified a critical decision window for change detection and revealed that mice use an adaptation-based rather than image-comparison strategy. This comprehensive resource provides a valuable substrate for understanding sensorimotor computations in neural networks.

neuroscience↗

bioRxiv2024

Secreted phospholipase PLA2G12A-driven lysophospholipid signaling via lipolytic modification of extracellular vesicles facilitates pathogenic Th17 differentiation

Lipogenesis-driven metabolic flux is crucial for differentiation of pathogenic Th17 cells. Although our previous CRISPR-based screening identified PLA2G12A as a key player in this process, it has remained obscure how this secreted phospholipase A2 isoform controls Th17 differentiation. Here we show that global, T cell-specific, or fibroblast-specific deletion of PLA2G12A prevents Th17 differentiation and associated diseases including psoriasis and arthritis. PLA2G12A acts on Th17-derived extracellular vesicles (EVs) to produce lysophospholipids including the ROR{gamma}t activator 1-oleoyl-lysophosphatidylethanolamine. These lysophospholipids are further converted by autotaxin to lysophosphatidic acid (LPA), which assists Th17 differentiation mainly via LPA2 receptor. Moreover, PLA2G12A promotes the secretion and uptake of EVs by Th17 cells and alters their cargo contents. Defective Th17 differentiation by PLA2G12A deficiency is rescued by supplementation with PLA2G12A-modified EVs. Importantly, a PLA2G12A-blocking antibody prevents Th17 differentiation and ameliorates psoriasis and arthritis models. Thus, targeting the PLA2G12A-EV-lysophospholipid axis may be useful for treatment of Th17-related diseases.

immunology↗

bioRxiv2023

SHIELD: Skull-shaped hemispheric implants enabling large-scale-electrophysiology datasets in the mouse brain

To understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. While new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe a novel 3D-printed cranial-replacement implant (SHIELD) enabling electrophysiological recordings from distributed areas of the mouse brain. This skull-shaped implant is designed with customizable insertion holes, allowing dozens of cortical and subcortical structures to be recorded in a single mouse using repeated multi-probe insertions over many days. We demonstrate the procedures high success rate, biocompatibility, lack of adverse effects on behavior, and compatibility with imaging and optogenetics. To showcase the scientific utility of the SHIELD implant, we use multi-probe recordings to reveal novel insights into how alpha rhythms organize spiking activity across visual and sensorimotor networks. Overall, this method enables powerful large-scale electrophysiological measurements for the study of distributed brain computation.

neuroscience↗

bioRxiv2022

A survey of neurophysiological differentiation across mouse visual brain areas and timescales

Neurophysiological differentiation (ND), a metric that quantifies the number of distinct activity states that the brain or its part visits over a period of time, has been used as a correlate of meaningfulness or subjective perception of visual stimuli. ND has largely been studied in non-invasive human whole-brain recordings where spatial resolution is limited. However, it is likely that perception is supported by discrete populations of spiking neurons rather than the whole brain. Therefore, in this study, we use Neuropixels recordings from the mouse brain to characterize the ND metric within neural populations recorded at single-cell resolution in localized regions. Using the spiking activity of thousands of simultaneously recorded neurons spanning 6 visual cortical areas as well as the visual thalamus, we show that the ND of stimulus-evoked activity of the entire visual cortex is higher for naturalistic stimuli relative to artificial ones. This finding holds in most individual areas throughout the visual hierarchy as well. For animals performing an image change detection task, ND of the entire visual cortex (though not individual areas) is higher for successful detection compared to failed trials, consistent with the assumed perception of the stimulus. Analysis of spiking activity allows us to characterize the ND metric across a wide range of timescales from 10s of milliseconds to a few seconds. This analysis reveals that although ND of activity of single neurons is often maximized at an optimal timescale around 100 ms, the optimum shifts to under 5 ms for ND of neuronal ensembles. Finally, we find that the ND of activations in convolutional neural networks (CNNs) trained on an image classification task shows distinct trends relative to the mouse visual system: ND is often higher for less naturalistic stimuli and varies by orders of magnitude across the hierarchy, compared to modest variation in the mouse brain. Together, these results suggest that ND computed on cellular-level neural recordings can be a useful tool highlighting cell populations that may be involved in subjective perception. SummaryAdvances in our understanding on neural coding has revealed that information about visual stimuli is represented across several brain regions. However, availability of information does not imply that it is necessarily utilized by the brain, much less that it is subjectively perceived. Since percepts originate in neural activity, distinct percepts must be associated with distinct states of neural activity, at least within the brain region that supports the percepts. Thus, one approach developed in this direction is to quantify the number of distinct states that the activity of the brain goes through, called neurophysiological differentiation (ND). ND of the entire brain has been shown to reflect subjective reports of visual stimulus meaningfulness. But what specific subpopulations within the brain could be supporting conscious perception, and what is the correct timescale on which states should be quantified? In this study, we analyze ND of spiking neural activity in the mouse visual cortex recorded using Neuropixels probes, allowing us to characterize the ND metric across a wide range of timescales all the way down from 5 ms to a few seconds. It also allows us to understand the ND of neural activity of different ensembles of neurons, from individual thalamic or cortical ensembles to those spanning across multiple visual areas in the mouse brain.

neuroscience↗

bioRxiv2020

Similar visual perception in GCaMP6 transgenic mice despite differences in learning and motivation

To study mechanisms of perception and cognition, neural measurements must be made during behavior. A goal of the Allen Brain Observatory is to map activity in distinct cortical cell classes during visual processing and behavior. Here we characterize learning and performance of five GCaMP6-expressing transgenic lines trained on a visual change detection task. We used automated training procedures to facilitate comparisons across mice. Training times varied, but most transgenic mice learned the task. Motivation levels also varied across mice. To compare mice in similar motivational states we subdivided sessions into over-, under-, and optimally motivated periods. When motivated, the pattern of perceptual decisions were highly correlated across transgenic lines, although overall d-prime was lower in one line labeling somatostatin inhibitory cells. These results provide important context for using these mice to map neural activity underlying perception and behavior.

neuroscience↗

bioRxiv2018

Biological variation in the sizes, shapes and locations of visual cortical areas in the mouse

Visual cortex is organized into discrete sub-regions or areas that are arranged into a hierarchy and serve different functions in the processing of visual information. In our previous work, we noted that retinotopic maps of cortical visual areas differed between mice, but did not quantify these differences or determine the relative contributions of biological variation and measurement noise. Here we quantify the biological variation in the size, shape and locations of 11 visual areas in the mouse. We find that there is substantial biological variation in the sizes of visual areas, with some visual areas varying in size by two-fold across the population of mice.

neuroscience↗