Neuroscience Research最新文献

Chemogenetics uses artificially-engineered proteins to modify the activity of cells, notably neurons, in response to small molecules. Although a common set of chemogenetic tools are the G protein-coupled receptor-based DREADDs, there has been great hope for ligand-gated, ion channel-type chemogenetic tools that directly impact neuronal excitability. We have devised such a technology by exploiting insect Ionotropic Receptors (IRs), a highly divergent subfamily of ionotropic glutamate receptors that evolved to detect diverse environmental chemicals. Here, we review a series of studies developing and applying this "IR-mediated neuronal activation" (IRNA) technology with the Drosophila melanogaster IR84a/IR8a complex, which detects phenyl-containing ligands. We also discuss how variants of IRNA could be produced by modifying the composition of the IR complex, using natural or engineered subunits, which would enable artificial activation of different cell populations in the brain in response to distinct chemicals.

The striatum consists of two anatomically and neurochemically distinct compartments, striosomes and the matrix, which receive dopaminergic inputs from the midbrain and exhibit distinct dopamine release dynamics in acute brain slices. Striosomes comprise approximately 15 % of the striatum by volume and are distributed mosaically. Therefore, it is difficult to selectively record dopamine dynamics in striosomes using traditional neurochemical measurements in behaving animals, and it is unclear whether distinct dynamics play a role in associative learning. In this study, we used transgenic mice selectively expressing Cre in striosomal neurons, combined with a fiber photometry technique, to selectively record dopamine release in striosomes during classical conditioning. Water-restricted mice could distinguish the conditioned stimulus (CS) associated with saccharin water from the air-puff-associated CS. The air-puff-associated CS evoked phasic dopamine release only in striosomes. Furthermore, air puff presentation induced dopamine release to striosomal neurons but suppressed release to striatal neurons non-selectively recorded. These findings suggest that dopamine is released in a differential manner in striosomes and the matrix in behaving animals and that dopamine release in striosomes is preferentially induced by the air-puff-associated CS and air puff presentation. These findings support the hypothesis that striosomal neurons play a dominant role in aversive stimuli prediction.

Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies.

Huntington's disease (HD) is a neurodegenerative disorder characterized by the presence of abnormally expanded polyglutamine tracts in huntingtin protein (HTT). Mutant HTT disrupts synaptic transmission and plasticity, particularly in the striatum and cortex, leading to early dysfunctions, such as altered neurotransmitter release, impaired synaptic vesicle recycling, and disrupted postsynaptic receptor function. Synaptic loss precedes neuronal degeneration and contributes to disease progression. Neurexin1 (NRXN1), a synaptic cell adhesion molecule primarily located in the presynaptic membrane, plays a crucial role in maintaining synaptic integrity. The present study investigated the role of NRXN1 in HD. This study researched whether the changed level has been related to expanded polyQ stretch and disease progression. Here, we report a reduction in NRXN1 levels in post-symptomatic HD mice and in neuronal cells expressing abnormally expanded polyQ tracts. Mutant HTT was found to decrease NRXN1 levels while increasing LAMP2A levels, which promotes lysosomal degradation of NRXN1. In HD cells expressing Q111, downregulated LAMP2A restored NRXN1 levels and maintained cell proliferation compared with cells expressing Q7. These findings suggest that NRXN1 is regulated by LAMP2A-mediated way and that decreased NRXN1 levels are associated with symptomatic progression and neuronal cell loss in HD.

Infrared laser stimulation of the cochlea has been proposed as a possible alternative to conventional auditory prostheses. Whereas previous studies have focused primarily on the short-term effects of laser stimulation, the practical application of this technics requires an investigation into whether prolonged laser exposure can induce neural responses and safely. This study assessed the effect of laser-induced damage to the cochlea on auditory perception using Mongolian gerbils (Meriones unguiculatus) trained with a classical conditioning task. The broadband noise was presented as a conditioned stimulus, and reward licking was recorded as a conditioned response. After training, the subject's cochlea was exposed to a continuous pulsed laser for 15 h. Broadband noise of various intensities was presented without pairing it with water before and after laser exposure to assess the decrease in auditory perception due to laser-induced injury. The licking rate did not change after laser exposure of 6.6 W/cm² or weaker but drastically decreased after 26.4 W/cm² or higher. These findings showed, for the first time, that the safety margin of long-term, at least several hours, cochlear laser stimulation exists and will contribute to the appropriate delimitation of the safe and effective laser stimulation parameters in future research.