Biology subjects

Sawada, M.

Publications and source records attributed to Sawada, M..

5 recordsLinked to original sources

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↗

bioRxiv2023

Temporally organized representations of reward and risk in the human brain

AO_SCPLOWBSTRACTC_SCPLOWThe value and uncertainty associated with choice alternatives constitute critical features along which decisions are made. While the neural substrates supporting reward and risk processing have been investigated, the temporal organization by which these computations are encoded remains elusive. Here we leverage the high spatiotemporal precision of intracranial electroencephalography (iEEG) to uncover how representations of decision-related computations unfold in time. We present evidence of locally distributed representations of reward and risk variables that are temporally organized across multiple regions of interest. Reward outcome representations across wide-spread regions follow a temporally cascading order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We highlight the role of the anterior insula in generalizing between reward prediction error (RePE) and risk prediction error (RiPE), within which the encoding of RePE in the distributed iEEG signal predicts RiPE. Together our results emphasize the utility of uncovering temporal dynamics in the human brain for understanding how computational processes critical for value-based decisions under uncertainty unfold.

neuroscience↗

bioRxiv2023

Optineurin provides a mitophagy contact site for TBK1 activation

Tank-binding kinase 1 (TBK1) is a Ser/Thr kinase involved in many intracellular processes including innate immunity, cell cycle, and apoptosis. TBK1 is also important for phosphorylating autophagy adaptors critical in selective autophagic removal of damaged mitochondria (mitophagy). However, the mechanism by which TBK1 is activated by PINK1/Parkin-mediated mitophagy remains largely unknown. Here, we show that the autophagy adaptor OPTN provides a unique platform for TBK1 activation. The OPTN-ubiquitin and OPTN-autophagy machinery interaction axes facilitate assembly of the OPTN-TBK1 complex at a contact site between damaged mitochondria and the autophagosome formation site. This assembly point serves as a positive feedback loop for TBK1 activation by accelerating hetero-autophosphorylation of the protein. Furthermore, expression of monobodies engineered in this study against OPTN impaired assembly of OPTN at the contact sites as well as the subsequent activation of TBK1 and mitochondrial degradation. Taken together the findings reveal that a positive reciprocal relationship between OPTN and TBK1 initiates autophagosome biogenesis on damaged mitochondria.

cell biology↗

bioRxiv2023

Reorganization of corticospinal projections after prominent recovery of finger dexterity from partial spinal cord injury in macaque monkeys

We investigated morphological changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in 7 macaque monkeys. All monkeys exhibited complete recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional (n = 4) and ipsilesional (n = 3) hand area of primary motor cortex (M1) were investigated at 5-29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and button-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gray matter around the lesion, and terminating in ipsilesional laminae VI/VII and IX were observed. In addition, axons and terminals from the ipsilesional M1 increased in the ipsilesional laminae VI/VII and IX after recrossing the midline, which were not observed in intact monkeys. Conversely, axons originating from the ipsilesional M1 and directed toward the contralesional laminae VI/VII and IX decreased. These results suggest that multiple reorganizations of the corticospinal projections to spinal segments both rostral and caudal to the lesion originating from bilateral M1 underlie a prominent recovery in long-term after spinal cord injury. SIGNIFICANCE STATEMENTPrevious studies have shown that dexterous finger movements recover prominently after lesion of the corticospinal tract (CST) at the mid-cervical segments through rehabilitative training in macaque monkeys. Here, we show reorganization of the CST including sprouting of axons originating from the contralesional and ipsilesional motor cortex in the gray matter both caudal and rostral to the lesion, including a re-direction of the CST to hand motoneurons in the monkeys 5-29 months after the lesion. Thus, multiple mechanisms of reorganization of CST axons underlie the recovery of impaired cortico-motoneuronal pathways for the long-term recovery of finger dexterity.

neuroscience↗

bioRxiv2022

Seg2Link: an efficient and versatile solution for semi-automatic cell segmentation in 3D image stacks

Recent advances in microscopy techniques, especially in electron microscopy, are transforming biomedical studies by acquiring large quantities of high-precision 3D cell image stacks. However, to study cell morphology and connectivity in organs such as brains, scientists must first perform cell segmentation, which involves extracting individual cell regions of various shapes and sizes from a 3D image. This remains a great challenge because automatic cell segmentation can contain numerous errors, even with advanced deep learning methods. For biomedical research that requires cell segmentation in large 3D image stacks, an efficient semi-automated software solution is still needed. We created Seg2Link, which generates automatic segmentations based on deep learning predictions and allows users to quickly correct errors in the segmentation results. It can perform automatic instance segmentation of 2D cells in each slice, 3D cell linking across slices, and various manual corrections, in order to efficiently transform inaccurate deep learning predictions into accurate segmentation results. Seg2Links data structure and algorithms were also optimized to process 3D images with billions of voxels on a personal computer quickly. Thus, Seg2Link offers a simple and effective way for scientists to study cell morphology and connectivity in 3D image stacks.

neuroscience↗