
도파민 신호 전달이 감각 인식을 목표 달성 근접성에 따라 편향시켜 경쟁 행동 간 우선순위를 결정한다.


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A state-dependent dopamine filter system in the&nbsp;male Drosophila brain&nbsp;balances threat perception against the drive to mate.

Mating proximity blinds threat perception - Nature

접근하는-교미-행동이-위협-인식을-방해한다


접근하는 교미 행동이 위협 인식을 방해한다


title_rewrite


UNC-6/네트린과 UNC-40/DCC는 축삭의 국소 접착과 방향성 성장을 모두 매개한다.


During development axons undergo long-distance migrations as instructed by guidance molecules and their receptors, such as UNC-6/Netrin and UNC-40/DCC. Guidance cues act through long-range diffusive gradients (chemotaxis) or local adhesion (haptotaxis). However, how these discrete modes of action guide axons in vivo is poorly understood. Using time-lapse imaging of axon guidance in C. elegans , we demonstrate that UNC-6 and UNC-40 are required for local adhesion to an intermediate target and subsequent directional growth. Exogenous membrane-tethered UNC-6 is sufficient to mediate adhesion but not directional growth, demonstrating the separability of haptotaxis and chemotaxis. This conclusion is further supported by the endogenous UNC-6 distribution along the axon’s route. The intermediate and final targets are enriched in UNC-6 and separated by a ventrodorsal UNC-6 gradient. Continuous growth through the gradient requires UNC-40, which recruitsUNC-6 to the growth cone tip. Overall, these data suggest that UNC-6 stimulates stepwise haptotaxis and chemotaxis in vivo .

### Competing Interest Statement

The authors have declared no competing interest.

UNC-6/Netrin promotes both adhesion and directed growth within a single axon

unc-6-네트린은-단일-축삭-내에서-접착과-방향성-성장을-모두-촉진한다


UNC-6/네트린은 단일 축삭 내에서 접착과 방향성 성장을 모두 촉진한다



인간 유래 유도만능줄기세포로부터 생성된 부착성 피질 소기관은 높은 재현성과 강력한 신경 활성을 나타내며, 이는 뇌 질환 모델링 및 치료제 스크리닝 응용에 큰 잠재력을 지닌다.


In the growing diversity of human iPSC-derived models of brain development, we present here a novel method that exhibits 3D cortical layer formation in a highly reproducible topography of minimal dimensions. The resulting adherent cortical organoids develop by self-organization after seeding frontal cortex patterned iPSC-derived neural progenitor cells in 384-well plates during eight weeks of differentiation. The organoids have stereotypical dimensions of 3 × 3 × 0.2 mm, contain multiple neuronal subtypes, astrocytes and oligodendrocyte lineage cells, and are amenable to extended culture for at least 10 months. Longitudinal imaging revealed morphologically mature dendritic spines, axonal myelination, and robust neuronal activity. Moreover, adherent cortical organoids compare favorably to existing brain organoid models on the basis of robust reproducibility in obtaining topographically-standardized singular radial cortical structures and circumvent the internal necrosis that is common in free-floating cortical organoids. The adherent human cortical organoid platform holds considerable potential for high-throughput drug discovery applications, neurotoxicological screening, and mechanistic pathophysiological studies of brain disorders.

### Competing Interest Statement

The authors have declared no competing interest.

Human adherent cortical organoids in a multiwell format

인간-유래-부착성-피질-소기관-다중-웰-포맷에서의-효율적-처리-및-분석


인간 유래 부착성 피질 소기관: 다중 웰 포맷에서의 효율적 처리 및 분석



이 연구는 해양 환형동물 Platynereis dumerilii 유생의 전신 시냅스 연결체를 재구성하여 전신 조정을 위한 신경 회로를 밝혀냈다.


Nervous systems coordinate effectors across the body during movements. We know little about the cellular-level structure of synaptic circuits for such body-wide control. Here we describe the whole-body synaptic connectome of a segmented larva of the marine annelid Platynereis dumerilii . We reconstructed and annotated over 9,000 neuronal and non-neuronal cells in a whole-body serial electron microscopy dataset. Differentiated cells were classified into 202 neuronal and 92 non-neuronal cell types. We analyse modularity, multisensory integration, left-right and intersegmental connectivity and motor circuits for ciliated cells, glands, pigment cells and muscles. We identify several segment-specific cell types, demonstrating the heteromery of the annelid larval trunk. At the same time, segmentally repeated cell types across the head, the trunk segments and the pygidium suggest the serial homology of all segmental body regions. We also report descending and ascending pathways, peptidergic circuits and a multi-modal mechanosensory girdle. Our work provides the basis for understanding whole-body coordination in an entire segmented animal.

### Competing Interest Statement

The authors have declared no competing interest.

Whole-body connectome of a segmented annelid larva

전체-연결체-지도로-살펴본-분절-환형동물-유생의-신경-회로


전체 연결체 지도로 살펴본 분절 환형동물 유생의 신경 회로



혈류는 성인 뇌에서 새로운 후각 구역 신경 세포의 이동을 촉진한다. 혈류 억제는 혈관 유도 신경 세포 이동을 감소시키며, 혈액에는 신경 세포 이동에 유익한 요인이 포함되어 있다.


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 improve the olfactory function for food-seeking behavior during starvation.

### Competing Interest Statement

The authors have declared no competing interest.

Neuronal migration depends on blood flow in the adult brain

성인-뇌에서-혈류가-신경-세포-이동에-의존한다


성인 뇌에서 혈류가 신경 세포 이동에 의존한다



신경 활동에 따른 아데노신 신호 전달이 성상 세포의 대사 활성화를 매개하여 뇌 기능 지원


This study explores how adenosine A2B receptors can act as astrocytic sensors&nbsp;of brain metabolic activity and how cAMP signalling in astrocytes may support core brain functions&nbsp;such as sleep and memory.

Adenosine signalling to astrocytes coordinates brain metabolism and function - Nature

신경-활동에-따른-아데노신-신호-전달이-성상-세포를-통해-뇌-대사와-기능을-조절한다


신경 활동에 따른 아데노신 신호 전달이 성상 세포를 통해 뇌 대사와 기능을 조절한다



선행 시냅스 Rac1 억제는 공간 작업 기억을 선택적으로 손상시키지만, 장기 기억에는 영향을 미치지 않는다.


One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory is selectively impaired following the expression of a genetically encoded Rac1-inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

### Competing Interest Statement

The authors have declared no competing interest.

Presynaptic Rac1 in the hippocampus selectively regulates working memory

선행-시냅스-rac1이-해마에서-작업-기억을-선택적으로-조절한다


선행 시냅스 Rac1이 해마에서 작업 기억을 선택적으로 조절한다



신경계 세포 유형 간 번역 조절 차이가 세포 유형 특이적 단백질 발현을 증폭시킨다.


Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically-defined cells in the Drosophila brain, we here revealed substantial posttranscriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias towards the 5′ leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open reading frames (uORFs) in the 5’ leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

### Competing Interest Statement

The authors have declared no competing interest.

Translational regulation enhances distinction of cell types in the nervous system

신경계-세포-유형-구분을-강화하는-번역-조절


신경계 세포 유형 구분을 강화하는 번역 조절



파리 디아파우스 과정에서 신경 발달 관련 유전자와 후각 신경 세포가 중요한 역할을 한다.


The effects of environmental stress on animal life are gaining importance with climate change. Diapause is a dormancy program that occurs in response to an adverse environment, followed by resumption of development and reproduction upon the return of favorable conditions. Diapause is a complex trait, so we leveraged the Drosophila genetic reference panel (DGRP) lines and conducted a Genome-Wide Association Study (GWAS) to characterize the genetic basis of diapause. We assessed post-diapause and non-diapause fecundity across all DGRP lines. GWAS revealed 546 genetic variants, encompassing single nucleotide polymorphisms, insertions and deletions associated with post-diapause fecundity. We identified 291 candidate diapause-associated genes, 40 of which had previously been associated with diapause. 89 of the candidates were associated with more than one SNP. Gene network analysis indicated that the diapause-associated genes were primarily linked to neuronal and reproductive system development. Similarly, comparison with results from other fly GWAS revealed the greatest overlap with olfactory-behavior-associated and fecundity-and-lifespan-associated genes. An RNAi screen of the top candidates identified two neuronal genes, Dip- γ and Scribbler, to be required during recovery for post-diapause fecundity. We complemented the genetic analysis with a test of which neurons are required for successful diapause. We found that although amputation of the antenna had little to no effect on non-diapause lifespan, it reduced diapause lifespan and postdiapause fecundity. We further show that olfactory receptor neurons and temperature-sensing neurons are required for successful recovery from diapause. Our results provide insights into the molecular, cellular, and genetic basis of adult reproductive diapause in Drosophila.

### Competing Interest Statement

The authors have declared no competing interest.

A genome-wide association study implicates the olfactory system in Drosophila melanogaster diapause-associated lifespan extension and fecundity

파리-디아파우스-관련-수명-연장-및-생식력-증가에-후각-시스템이-관여한다는-유전체-연관-연구


파리 디아파우스 관련 수명 연장 및 생식력 증가에 후각 시스템이 관여한다는 유전체 연관 연구



신경 활동 수준의 변화가 GABAergic 시냅스 가소성을 유발하며, 이는 신경 흥분성 조절에 중요한 역할을 할 수 있다.


Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations in vivo have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here we show results that GABAergic scaling can act to homeostatically control spiking levels. We found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPAR or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling.

Significance Statement The nervous system maintains excitability in order to perform network behaviors when called upon to do so. Networks are thought to maintain spiking levels through homeostatic synaptic scaling, where compensatory multiplicative changes in synaptic strength are observed following alterations in cellular spike rate. Although we demonstrated that AMPAergic synaptic scaling does not appear meet these criteria as a spike rate homeostat, we now show that GABAergic scaling could play this role. Here we present evidence that the characteristics of GABAergic scaling place it in an excellent position to be a spiking homeostat. This work highlights the importance of inhibitory circuitry in the homeostatic control of excitability. Further, it provides a point of focus into neurodevelopmental disorders where excitability is impaired.

### Competing Interest Statement

The authors have declared no competing interest.

GABAergic synaptic scaling is triggered by changes in spiking activity rather than AMPA receptor activation

신경-활동-변화에-따른-gabaergic-시냅스-가소성-유발


신경 활동 변화에 따른 GABAergic 시냅스 가소성 유발
