Biology subjects

Eguchi, K.

Publications and source records attributed to Eguchi, K..

5 recordsLinked to original sources

bioRxiv2026

Somatic Cx36 gap junctions expand the anatomical substrate for electrical coupling in the adult mouse inferior olive

The inferior olive (IO) is unique among adult mammalian brain nuclei in that its neurons communicate solely via gap junctions. For more than half a century, models of cerebellar timing, synchrony, and learning have therefore centered on how electrical coupling between olivary neurons is regulated. In the prevailing anatomical model, IO gap junctions reside on dendritic spines within olivary glomeruli, where nearby inhibitory terminals can locally regulate coupling through shunting conductances. Here we show that this view is incomplete. In the adult mouse IO, closely apposed neuronal somata are common, direct soma-soma appositions are visible by volume electron microscopy, Cx36 puncta occur at somatic contacts, and freeze-fracture replica labeling identifies Cx36-associated gap junction plaques on large continuous membrane surfaces. These soma-proximal gap junctions extend olivary electrical coupling beyond dendritic-spine glomeruli, challenging a core anatomical assumption in models of cerebellar coordination.

neuroscience↗

bioRxiv2024

Photodynamic Therapy for Deep Organ Cancer by Implantable Wireless OLEDs

Metronomic photodynamic therapy (mPDT) is a method of continuously delivering low-intensity light to a cancer lesion. Since high light intensity is not required, the light device can be miniaturized and implanted in the body. Nevertheless, for clinical implementation, it is essential to develop a light source apparatus that can effectively illuminate the entire tumor and operate stably without damaging internal organs. To address this issue, an organic light-emitting diode (OLED) optical device that has an area large enough to cover the entire lesion and is powered by a wireless power supply has been developed. The device is thin and lightweight and it functioned stably in the abdominal cavity of rats for more than two weeks without causing foreign body reactions. By covering the tumor site of rat liver cancer with this device and continuously illuminating the tumor with appropriate administration of a photosensitizer, the entire tumor under the emitting surface was eliminated through apoptosis without leaving any residual tumor margins. This is the first report of a robust antitumor effect on parenchymal organ cancers by mPDT using a biocompatible, wirelessly powered OLED device, which represents a potential new deep organ cancer therapy.

bioengineering↗

bioRxiv2022

Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons

Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role in neuronal activities through interaction with various proteins involved in signaling at membranes. However, the distribution pattern of PI(4,5)P2 and the co-clustering with these proteins on the neuronal cell membranes remain elusive at the electron microscopic level. In this study, we quantitatively investigated the nanoscale distribution of PI(4,5)P2 on the neuronal cell membranes by SDS-digested freeze-fracture replica labeling with cryo-fixed mouse cerebellum. We demonstrate that PI(4,5)P2 makes clusters with a mean size of [~] 1,000 nm2 and these clusters show preferential accumulation in specific membrane compartments depending on cell types. Purkinje cell (PC) spines and granule cell (GC) presynaptic active zones are particularly rich in the PI(4,5)P2 clusters. Furthermore, these clusters are extensively associated with clusters of CaV2.1 and GIRK3 throughout different membrane compartments of PCs, GCs, and molecular layer interneurons. In contrast, these clusters showed compartment-specific association with mGluR1 in PC spines. These results suggest that visualization of the nanoscale PI(4,5)P2 distribution may provide insight into the physiological functions of PI(4,5)P2 in neurons.

neuroscience↗

bioRxiv2021

Microtubule assembly by soluble tau impairs vesicle endocytosis and excitatory neurotransmission via dynamin sequestration in Alzheimer's disease synapse model

Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in Alzheimers disease. We addressed whether tau elevation affects synaptic transmission at the calyx of Held in brainstem slices. Whole-cell loading of WT human tau (h-tau) in presynaptic terminals at 10-20 {micro}M caused microtubule (MT) assembly and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking MT assembly using nocodazole prevented tau-induced impairments of endocytosis and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly by WT h-tau loading was associated with an increased bound fraction of the endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin-1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced impairments of endocytosis and neurotransmission. We conclude that elevation of presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired, causing activity-dependent rundown of neurotransmission. Significance StatementWild-type human recombinant tau loaded in rodent presynaptic terminals inhibited vesicle endocytosis, thereby causing activity-dependent rundown of excitatory transmission. This endocytic block is caused by a sequestration of dynamin by excess microtubules newly assembled by tau and can be rescued by a peptide inhibiting the microtubules-dynamin interaction, or by the microtubule disassembler nocodazole. Thus, synaptic dysfunction can be induced by pathological increase of endogenous soluble tau in Alzheimer disease slice model.

neuroscience↗

bioRxiv2019

Advantages of acute brain slices prepared at physiological temperature in characterization of synaptic functions

Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability and higher detectability of long-term depression after motor learning compared with slices prepared at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.

neuroscience↗