Biology subjects

Nabekura, J.

Publications and source records attributed to Nabekura, J..

6 recordsLinked to original sources

bioRxiv2026

Astrocyte stimulation reopens the window of the critical period for the experience-dependent plasticity of retinogeniculate synapses

A specific time window during which neural circuits undergo dramatic changes in response to individual experiences is known as the critical period (CP). Developing methods to reopen the CP after its closure could lead to the establishment of effective treatment approaches. The retinogeniculate (RG) synapses in the dorsal lateral geniculate nucleus (dLGN) undergo experience-dependent remodeling only during the limited period of development. We investigated the effects of astrocyte manipulation on the restoration of RG synapse plasticity after the CP termination. Astrocytic stimulation with the designer receptors exclusively activated by designer drugs (DREADD) after the CP closure caused RG synapse remodeling in the dark-reared mice but not in those reared in normal conditions. Single-nucleus RNA sequencing (snRNA-seq) of dLGN astrocytes implicated the underlying mechanisms of astrocyte-induced RG synaptic plasticity. Therefore, astrocytes can regulate the susceptibility of RG synapses to experience-dependent plasticity after CP termination.

neuroscience↗

bioRxiv2025

In vivo deep-brain microscopy at submicrometer resolution with refractive index-matched prism interfaces

The mammalian brain is a thick and densely layered structure comprising a huge number of neurons that work together to process information and regulate brain functions. Although various optical methods have been developed to investigate deep brain dynamics, they are limited by technical constraints, invasiveness, suboptimal spatial resolution, and/or a restricted field of view. To overcome these limitations, we developed an implantable, optically optimized microprism interface with a refractive index matched to that of brain tissue and water, enabling minimally-invasive, wide-field two-photon imaging method with enhanced brightness and sub-micron resolution in deep prefrontal areas.

neuroscience↗

bioRxiv2024

Low-invasive, wide-field, and cellular resolution two-photon imaging of neural population activity in brainstem and nucleus tractus solitarii

Brain-viscera communication plays a crucial role in regulating mental health, with the vagus nerve being a key structure mediating this interaction. Clinically, artificial vagus nerve stimulation (VNS) is used to treat various neuropsychiatric disorders, highlighting the importance of vagal afferent fibers in regulating emotion. The nucleus tractus solitarii (NTS) is a brainstem structure proposed to receive signals from vagal afferents and relay them to brain networks for emotion regulation. However, due to the anatomical complexity and difficulty in accessing the deep-brain NTS region in living animals, the mechanisms remain unclear. Here, we developed a wide-field and deep-brain two-photon imaging method using a double-prism based optical interface. This approach enables the identification of cellular-resolution neural activities in the NTS while preserving the cerebellum, which covers the NTS and is important for emotion regulation, intact. We systematically evaluated how NTS neurons respond to VNS and a gastrointestinal hormone, suggesting the usefulness of this method for investigating the role of the vagus-NTS pathway in vivo.

neuroscience↗

bioRxiv2024

Neuronal migration depends on blood flow in the adult brain

In animal tissues, several cell types migrate along blood vessels, raising the possibility that blood flow influences cell migration. Here, we show that blood flow promotes the migration of new olfactory-bulb neurons in the adult brain. Neuronal migration is facilitated by blood flow, leading to accumulation of new neurons near blood vessels with abundant blood flow. Blood flow inhibition attenuates blood vessel-guided neuronal migration, suggesting that blood contains factors beneficial to neuronal migration. We found that ghrelin, which is increased in blood by hunger, directly influences neuronal migration. Ghrelin signaling promotes somal translocation by activating actin cytoskeleton contraction at the rear of the cell soma. New neurons mature in the olfactory bulb and contribute to the olfactory function for sensing odorants from food. Finally, we show that neuronal migration is increased by calorie restriction, and that ghrelin signaling is involved in the process. This study suggests that blood flow promotes neuronal migration through blood-derived ghrelin signaling in the adult brain, which could be one of the mechanisms that improves the olfactory function for food-seeking behavior during starvation.

neuroscience↗

bioRxiv2021

Optical and computational dissection of emergent prefrontal rewiring to encode fear memory

Associative learning is crucial for adapting to environmental changes. The encoding of associative learning involves the dorso-medial prefrontal cortex (dmPFC), and is underpinned by interactions within the resident neuronal population. However, the nature of this population coding is poorly understood. Here we developed a pipeline for computational dissection and longitudinal two-photon imaging of neural population activities in the mouse dmPFC during fear-conditioning procedures, enabling us to detect learning-dependent changes in the dmPFC topology. Through regularized regression methods and graphical modeling, we found fear conditioning organized neuronal ensembles encoding conditioned responses (CR), with enhancing their coactivity, functional connectivity, and association with conditioned stimuli (CS). This suggests that fear conditioning drives dmPFC reorganization to generate novel associative circuits for CS-to-CR transformation. Importantly, neurons strongly responding to unconditioned stimuli (US) during conditioning anterogradely became a hub of the CR ensemble. Altogether, we demonstrate learning-dependent dynamic modulation of population coding structured on an activity-dependent hub-network formation within the dmPFC. TeaserOptical and computational dissection uncovered how prefrontal cortical networks are rewired to encode new associative memory Significance statementAnimals learn to adapt to changing environments. Associative learning is one of the simplest types of learning that has been intensively studied over the past century. Recent development in molecular, genetic, and optogenetic methods has enabled the identification of a neural population encoding the associative memory in the brain. However, it remains unclear how information is stored and processed by the neural population to encode and retrieve the associative memory. To investigate the nature of this population coding, we developed an optical and computational dissection method, demonstrating how associative learning drives reorganization of the neural network in the dorso-medial prefrontal cortex and generates novel circuits for associative memory and signal transformation.

neuroscience↗

bioRxiv2018

Conditional upregulation of KCC2 selectively enhances neuronal inhibition during seizures

Abstract/SummaryEfficacious neuronal inhibition is sustained by the neuronal K+Cl- co-transporter KCC2, and loss of KCC2 function through injury or mutation is associated with altered GABAergic signalling and neuronal seizures. Here we report a transgenic mouse with conditional KCC2 overexpression that results in increased membrane transport function. Increased KCC2 has little impact on behavioural and in vitro assays of neuronal excitability and GABAA receptor responses under resting conditions. In contrast, increased KCC2 imparts resistance to seizure-like neuronal activity in hippocampal slices and prevents the progression of mice into behavioural status epilepticus following multiple kainic acid doses. Our results demonstrate a transgenic mouse to facilitate investigations into the role of KCC2 in brain function, and provide a proof of principle that targeting KCC2 may be an effective way to selectively enhance neuronal inhibition to mitigate against diseases that involve an imbalance between excitation and inhibition.

neuroscience↗