Biology subjects

Suematsu, N.

Publications and source records attributed to Suematsu, N..

6 recordsLinked to original sources

bioRxiv2025

Chronic alteration of Ca2+ and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice

Understanding the chronic effects of intracortical microstimulation (ICMS) and device implantation on cortical function is essential for the development of stable neuroprosthetics. We chronically implanted microelectrode into Thy1-GCaMP6s mice and conducted longitudinal mesoscopic widefield and two-photon Ca2#x002B; imaging alongside intrinsic optical signal recordings over 12 weeks. Six ICMS frequencies (10-500 Hz) and contralateral visual LED stimuli were delivered in repeated sessions. Oxygen extraction fraction (OEF) was estimated from dual-wavelength reflectance, and hemodynamic response functions (HRF) were derived via regularized deconvolution. Over the chronic period, 25-Hz ICMS evoked progressively larger Ca2+ responses whose duration was extending, while spatial spread remained stable around 500 {micro}m. Concurrently, OEF reductions deepened, reflecting increased relative blood supply, and the spatial extent of OEF signals contracted in the first week before expanding by day 21. After discharge-like Ca2+ events emerged in nearly half of mice, predominantly under 25-Hz ICMS. HRF peak amplitude increased between day 0 and days 7-21, with latency decreasing. Chronic ICMS induces progressive potentiation of neuronal and vascular responses alongside local neurovascular uncoupling on day 0 and sustained silencing of spontaneous activity near the implant. These dynamics exhibiting a stabilization 6-7 weeks after the implantation, coupled with frequency-dependent after discharges, underscore the need for adaptive stimulation strategies prior to the stabilization and to prevent the after discharge and implant designs that mitigate local suppression and ensure long-term stability of cortical neuroprostheses.

bioengineering↗

bioRxiv2025

Aging diminishes interlaminar functional connectivity in the mouse cortical V1 and CA1 hippocampal regions

Aging disrupts brain network integration and is a significant risk factor for cognitive decline and neurological diseases, yet the circuit-level mechanisms underlying these changes remain unclear. Most previous studies have utilized cross-sectional or acute approaches, limiting insights into the longitudinal dynamics of the neural network. In this study, we chronically recorded laminar electrophysiological activity in both the primary visual cortex (V1) and hippocampal CA1 region of young (2-month-old) and aged (13-month-old) mice over 16 weeks. This approach allowed us to directly assess how aging modulates functional connectivity within hierarchically connected cortical and hippocampal circuits. We found that single-unit spiking activity and the signal-to-noise ratio were largely preserved in aged versus young mice, suggesting intact neuronal firing properties. However, aged mice showed global reductions in local field potential (LFP) power and a selective decrease in coherence across delta, alpha-beta, and gamma frequency bands within and between cortical layers and V1-CA1 pathways, while phase amplitude coupling remained unaffected. Interestingly, population level excitatory activity in CA1 was increased in aged animals. These findings indicate that aging selectively impairs network-level synchrony and temporal coordination in specific frequency bands and regions, with minimal loss of single-neuron function. Our results highlight the necessity of longitudinal, multi-region measurements to uncover the multi-scale vulnerabilities of the aging brain. Understanding the depth- and region-dependent circuit changes will guide strategies to preserve cortical-hippocampal communication and cognitive function in aging, as well as enhance neural interface technologies for older populations. NEW & NOTEWORTHYAging non-uniformly degrades cortico-hippocampal networks, leading to region- and frequency-specific breakdowns in coordinated activity. While single-neuron activity remains preserved, disruptions in frequency-selective synchrony (delta and alpha-beta) were observed in aged mice, indicating impaired V1-CA1 communication as a marker of aging rather than neuronal degeneration. By separating single-neuron activity and large-scale dynamics, we reveal that aging alters communication between sensory and memory systems, underscoring the need for longitudinal approaches to capture age-related impairments in laminar connectivity.

neuroscience↗

bioRxiv2025

AgRP Neuronal Suppression by Spontaneous Movement Encodes Exercise Reinforcement

Hypothalamic agouti-related peptide (AgRP) neurons that drive hunger-related behaviors are activated during energy deficit, encode negative valence but can be inhibited even by perception of food without digestion. Here, we show that in head-fixed mice, discrete motor actions such as spontaneous walking and conditioned licking rapidly suppress AgRP neuron activity. This suppression persisted throughout movement and terminated upon cessation, which was independent of food perception or conditioned cues. The degree of suppression was positively correlated with movement vigor. While optogenetic enhancement of AgRP neuron suppression did not initiate movement, it promoted reinforcement of concurrent walking behavior. These findings unmask that spontaneous, low intensity physical activity can reduce AgRP neuron activity reinforcing concurrent movement/exercise with implications for systemic health benefits.

neuroscience↗

bioRxiv2025

Hypermyelination Improves Strength and Detection of Neuronal Activity in the CA1 Hippocampus and Facilitates Neuroprotection in FusOLcKO Mice

1.0.Loss of oligodendrocytes (OLs) and myelin impairs cortical neuronal firing and network stability, whereas enhancement of oligodendrogenesis improves electrophysiological stability in cortex and, to a lesser extent, hippocampus. OLs exhibit regional heterogeneity, especially in their ability to synthesize cholesterol, a critical driver of myelin wrapping and ensheathment of axons. Conditional depletion of the Fused in sarcoma (Fus) gene in OLs, referred to as FusOLcKO, increases cholesterol biosynthesis, myelin thickness, and tissue cholesterol content. We examine whether this hypermyelination alters extracellular recordings across the layers of visual cortex and the underlying hippocampal CA1 over 16 weeks. In FusOLcKO mice, visually-evoked single-unit detectability and firing rate in CA1 increased relative to wild-type littermates, whereas cortical recordings showed no improvement. At the population level, FusOLcKO cortex exhibited reduced firing rates and lower functional connectivity, indicating altered network dynamics. Post-mortem histology revealed higher neuron density in recorded cortex and greater excitatory synapse density in CA1 of FusOLcKO mice suggesting region-specific neuroprotection and synaptic strengthening. These results demonstrate that cholesterol-driven hypermyelination enhances chronic hippocampal recordings while disrupting cortical network communication. Our study highlights myelins region-dependent roles in supporting single-cell reliability, tuning population dynamics, and maintaining circuit integrity under chronic perturbation. 2.0. SIGNIFICANCE STATEMENTMyelin critically regulates neural circuit function via conduction and metabolic support. Here, we show that cholesterol-driven hypermyelination in FusOLcKO mice augments single-unit detection and firing in hippocampal CA1 but reduces population firing and interlaminar connectivity within the cortex. These findings reveal a dual role for myelin: it can both safeguard specific circuit activity and perturb large-scale cortical communication. Understanding these dynamics is essential for designing myelin-targeted therapies in neurodegenerative disorders.

neuroscience↗

bioRxiv2024

Activation and depression of neural and hemodynamic responses induced by the intracortical microstimulation and visual stimulation in the mouse visual cortex.

Objective. Intracortical microstimulation can be an effective method for restoring sensory perception in contemporary brain-machine interfaces. However, the mechanisms underlying better control of neuronal responses remain poorly understood, as well as the relationship between neuronal activity and other concomitant phenomena occurring around the stimulation site. Approach. Different microstimulation frequencies were investigated in vivo on Thy1-GCaMP6s mice using widefield and two-photon imaging to evaluate the evoked excitatory neural responses across multiple spatial scales as well as the induced hemodynamic responses. Specifically, we quantified stimulation-induced neuronal activation and depression in the mouse visual cortex and measured hemodynamic oxyhemoglobin and deoxyhemoglobin signals using mesoscopic-scale widefield imaging. Main results. Our calcium imaging findings revealed a preference for lower-frequency stimulation in driving stronger neuronal activation. A depressive response following the neural activation preferred a slightly higher frequency stimulation compared to the activation. Hemodynamic signals exhibited a comparable spatial spread to neural calcium signals. Oxyhemoglobin concentration around the stimulation site remained elevated during the post-activation (depression) period. Somatic and neuropil calcium responses measured by two-photon microscopy showed similar dependence on stimulation parameters, although the magnitudes measured in soma was greater than in neuropil. Furthermore, higher-frequency stimulation induced a more pronounced activation in soma compared to neuropil, while depression was predominantly induced in soma irrespective of stimulation frequencies. Significance. These results suggest that the mechanism underlying depression differs from activation, requiring ample oxygen supply, and affecting neurons. Our findings provide a novel understanding of evoked excitatory neuronal activity induced by intracortical microstimulation and offer insights into neuro-devices that utilize both activation and depression phenomena to achieve desired neural responses.

bioengineering↗

bioRxiv2022

Hippocampal CA1 represents action and reward events instantly compared to the superficial and deep layers of the lateral entorhinal cortex

The entorhinal cortex (EC) is the main interface between the hippocampus and the neocortex. The EC plays a critical role in learning and memory. We investigated the neuronal representation of behavioral events during operant learning in the hippocampal-entorhinal circuit of head-fixed rats. Both CA1 and lateral entorhinal cortex (LEC) neurons develop task-related activities after learning. Among diverse task-related activities, we compared the transient peak activities that represent action and reward and found a distinct difference in the timing of behavioral event representation between CA1 and LEC. CA1 represents action and reward events in close to real-time, whereas both the superficial and deep layers of the LEC showed delayed representation of those events. Our results suggest that subpopulations exist within which CA1 and LEC neurons process the information in a different order from the anatomically defined hippocampal-entorhinal circuit.

neuroscience↗