Plasticity is the key feature of our brain function. Specifically, plasticity of hippocampal synapses is critical for learning and memory. The functional properties of the neuronal circuit change as a result of synaptic plasticity. This review summarizes the use of voltage-sensitive dyes (VSDs) to examine neuronal circuit plasticity. We will discuss the significance of plastic changes in circuit function as well as the technical issue of using VSDs. Further, we will discuss the neural circuit level plasticity of the hippocampus caused by long-term potentiation and the entorhinal-perirhinal connection. This review article is an extended version of the Japanese article, Membrane Potential Imaging with Voltage-sensitive Dye (VSD) for Long-term Recording, published in SEIBUTSU BUTSURI Vol. 61, p. 404-408 (2021).
Much effort has been devoted to elucidate mechanisms of amyloid fibril formation using various kinds of additives, such as salts, metals, detergents, and biopolymers. Here, we review the effects of additives with a focus on polyphosphate (polyP) on amyloid fibril formation of β2-microglobulin (β2m) and α-synuclein (αSyn). PolyP, consisting of up to 1,000 phosphoanhydride bond-linked phosphate monomers, is one of the most ancient, enigmatic, and negatively charged molecules in biology. Amyloid fibril formation of both β2m and αSyn could be accelerated by counter anion-binding and preferential hydration at relatively lower and higher concentrations of polyP, respectively, depending on the chain length of polyP. These bimodal concentration-dependent effects were also observed in salt- and heparin-induced amyloid fibril formation, indicating the generality of bimodal effects. We also address the effects of detergents, alcohols, and isoelectric point precipitation on amyloid fibril formation, in comparison with the effects of salts. Because polyP is present all around us, from cellular components to food additives, clarifying its effects and consequent biological roles will be important to further advance our understanding of amyloid fibrils. This review article is an extended version of the Japanese article, Linking Protein Folding to Amyloid Formation, published in SEIBUTSU BUTSURI Vol. 61, p. 358-365 (2021).
While it is often believed that the origins of life required participation of early biomolecules, it has been recently proposed that "non-biomolecules", which would have been just as, if not more, abundant on early Earth, could have played a part. In particular, recent research has highlighted the various ways by which polyesters, which do not participate in modern biology, could have played a major role during the origins of life. Polyesters could have been synthesized readily on early Earth through simple dehydration reactions at mild temperatures involving abundant "non-biological" alpha hydroxy acid (AHA) monomers. This dehydration synthesis process results in a polyester gel, which upon further rehydration, can assemble into membraneless droplets proposed to be protocell models. These proposed protocells can provide functions to a primitive chemical system, such as analyte segregation or protection, which could have further led to chemical evolution from prebiotic chemistry to nascent biochemistry. Here, to further shed light into the importance of "non-biomolecular" polyesters at the origins of life and to highlight future directions of study, we review recent studies which focus on primitive synthesis of polyesters from AHAs and assembly of these polyesters into membraneless droplets. Specifically, most of the recent progress in this field in the last five years has been led by laboratories in Japan, and these will be especially highlighted. This article is based on an invited presentation at the 60th Annual Meeting of the Biophysical Society of Japan held in September, 2022 as an 18th Early Career Awardee.
Near-field scanning optical microscopy (NSOM) is a super-resolution optical microscopy based on nanometrically small near-field light at a metallic tip. It can be combined with various types of optical measurement techniques, including Raman spectroscopy, infrared absorption spectroscopy, and photoluminescence measurements, which provides unique analytical capabilities to a variety of scientific fields. In particular, to understand nanoscale details of advance materials and physical phenomena, NSOM has been often adopted in the fields of material science and physical chemistry. However, owing to the recent critical developments showing the great potential for biological studies, NSOM has also recently gained much attention in the biological field. In this article, we introduce recent developments made in NSOM, aiming at biological applications. The drastic improvement in the imaging speed has shown a promising application of NSOM for super-resolution optical observation of biological dynamics. Furthermore, stable imaging and broadband imaging were made possible owing to the advanced technologies, which provide a unique imaging method to the biological field. As NSOM has not been well exploited in biological studies to date, several rooms need to be explored to determine its distinct advantages. We discuss the possibility and perspective of NSOM for biological applications. This review article is an extended version of the Japanese article, Development of Near-field Scanning Optical Microscopy toward Its Application for Biological Studies, published in SEIBUTSU BUTSURI Vol. 62, p. 128-130 (2022).
Mitochondria play an important role in energy conversion as well as in intracellular calcium (Ca2+) storage. Ca2+ uptake from the cytosol to the mitochondria is mediated by the calcium uniporter, which functions as a Ca2+ ion channel. However, the molecular composition of this uniporter has remained unclear until recently. The Ca2+ ion channel consists of seven subunits. The yeast reconstitution technique revealed that the mitochondrial calcium uniporter (MCU) and essential MCU regulatory element (EMRE) are the core subunits of the complex. Furthermore, detailed structure-function analyses of the core subunits (MCU and EMRE) were performed. In this review, the regulatory mechanism of mitochondrial Ca2+ uptake is discussed.