Biology subjects

Kuwabara, M.

Publications and source records attributed to Kuwabara, M..

4 recordsLinked to original sources

bioRxiv2025

Paralemmin-3 sustains the integrity of the lateral plasma membrane and subsurface cisternae of auditory hair cells

In the mammalian inner ear, cochlear inner hair cells (IHCs) enable accurate and faithful synaptic sound encoding, while outer hair cells (OHCs) perform frequency-specific sound amplification and fine-tuning through their intrinsic voltage-dependent somatic electromotility. This latter process is facilitated by the unique trilaminate structure of the OHC lateral wall, which consists of the plasma membrane that is densely occupied by the transmembrane motor protein Prestin, the submembrane actin- and spectrin-based cytoskeleton, and the endomembranous subsurface cisternae. This complex system provides mechanical resilience while allowing for cell expansion and contraction during electromotility. Whereas the ultrastructure of the lateral wall is well described, its molecular architecture remains largely elusive. Here, we identified Paralemmin-3 (Palm3) as a novel protein specifically localized to the lateral walls of auditory HCs to play a crucial role in connecting the plasma membrane to the underlying cytoskeleton and subsurface cisternae. Palm3-KO mice display early-onset and progressive hearing impairment that results from diminished cochlear amplification. Subsequent multiscale morphological analyses revealed structural collapse of OHCs that led to progressive and extensive OHC loss along the tonotopic axis. Palm3-KO OHCs exhibited disrupted expression and distribution of several membrane-associated proteins - including spectrin isoforms and Prestin - suggesting an essential role of Palm3 in plasma membrane scaffolding. Electron tomography of OHC lateral walls revealed significantly fewer and structurally perturbed subsurface cisternae. Finally, adeno-associated virus (AAV)-mediated rescue of Palm3 during early postnatal development partly restored hearing function, enhanced OHC survival, and restored OHC cell shape as well as membrane protein expression levels. In summary, Palm3 is a key component of the submembrane cytoskeleton in cochlear hair cells, playing a fundamental role in hair cell biology and hearing, and emerges as an attractive candidate for the long-elusive "pillar" component of the hair cell lateral wall ultrastructure.

cell biology↗

bioRxiv2023

A Deep Learning Approach to Detecting Temporal Characteristics of Cortical Regions

One view of the neocortical architecture is that every region functions based on a universal computational principle. Contrary to this, we postulated that each cortical region has its own specific algorithm and functional properties. This idea led us to hypothesize that unique temporal patterns should be associated with each region, with the functional commonalities and variances among regions reflecting in the temporal structure of their neural signals. To investigate these hypotheses, we employed deep learning to predict electrodes locations in the macaque brain using single-channel ECoG signals. To do this, we first divided the brain into seven regions based on anatomical landmarks, and trained a deep learning model to predict the electrode location from the ECoG signals. Remarkably, the model achieved an average accuracy of 33.6%, significantly above the chance level of 14.3%. All seven regions exhibited above-chance prediction accuracy. The models feature vectors identified two main clusters: one including higher visual areas and temporal cortex, and another encompassing the remaining other regions.These results bolster the argument for unique regional dynamics within the cortex, highlighting the diverse functional specializations present across cortical areas.

neuroscience↗

bioRxiv2021

Tandem mass spectrum similarity-based network analysis using 13C-labeled and non-labeled metabolome data to identify the biosynthesis pathway of the blood pressure-lowering asparagus metabolite asparaptine A

Asparaptine, a conjugate of arginine and asparagusic acid, was found in asparagus (Asparagus officinalis) as a naturally occurring inhibitor of angiotensin-converting enzyme (ACE) in vitro. The biosynthetic pathway to asparaptine is largely unknown; however, it is suggested that asparagusic acid may be biosynthesized from valine. To determine which metabolites are involved in the asparaptine biosynthetic pathway, we performed tandem mass spectrometry similarity-based metabolome network analysis using 13C labeled and non-labeled valine-fed asparagus calluses. We determined that valine is used as a starting material, S(2-carboxy-n-propyl)-cysteine as an intermediate, and two new metabolites as asparaptine analogs, lysine- and histidine-type conjugates, are involved in the pathway. Asparaptine was therefore renamed asparaptine A (arginine type), and the two analogs were named asparaptines B (lysine type) and C (histidine type). Oral feeding of asparaptine A to a hypertensive mouse species showed that this metabolite lowers both blood pressure and heart rate within two hours and both of which were back to normal two days later. These results suggest that asparaptine A may not only have effects as an ACE inhibitor, but also has {beta}-antagonistic effects, which are well-known to be preventive for cardiovascular diseases.

plant biology↗

bioRxiv2019

Neural Mechanisms of Economic Choices in Mice

Economic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of cells encoded the values of individual options, the binary choice outcome and the chosen value. These groups match those previously identified in primates, except that the neuronal representation in mice is spatial (in monkeys it is good-based). Our results lay the foundations for a circuit-level analysis of economic decisions.

neuroscience↗