scholarly journals Analysis of growth cone extension in standardized coordinates highlights self-organization rules during wiring of the Drosophila visual system

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009857
Author(s):  
Weiyue Ji ◽  
Lani F. Wu ◽  
Steven J. Altschuler

A fascinating question in neuroscience is how ensembles of neurons, originating from different locations, extend to the proper place and by the right time to create precise circuits. Here, we investigate this question in the Drosophila visual system, where photoreceptors re-sort in the lamina to form the crystalline-like neural superposition circuit. The repeated nature of this circuit allowed us to establish a data-driven, standardized coordinate system for quantitative comparison of sparsely perturbed growth cones within and across specimens. Using this common frame of reference, we investigated the extension of the R3 and R4 photoreceptors, which is the only pair of symmetrically arranged photoreceptors with asymmetric target choices. Specifically, we found that extension speeds of the R3 and R4 growth cones are inherent to their cell identities. The ability to parameterize local regularity in tissue organization facilitated the characterization of ensemble cellular behaviors and dissection of mechanisms governing neural circuit formation.

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Abhishek Kulkarni ◽  
Deniz Ertekin ◽  
Chi-Hon Lee ◽  
Thomas Hummel

The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.


2020 ◽  
Author(s):  
Alexandre Dumoulin ◽  
Nikole R. Zuñiga ◽  
Esther T. Stoeckli

ABSTRACTDuring neural circuit formation, axons navigate several choice points to reach their final target. At each one of these intermediate targets, growth cones need to switch responsiveness from attraction to repulsion in order to move on. Molecular mechanisms that allow for the precise timing of surface expression of a new set of receptors that support the switch in responsiveness are difficult to study in vivo. Mostly, mechanisms are inferred from the observation of snapshots of many different growth cones analyzed in different preparations of tissue harvested at distinct time points. However, to really understand the behavior of growth cones at choice points, a single growth cone should be followed arriving at and leaving the intermediate target.Here, we describe a spinal cord preparation that allows for live imaging of individual axons during navigation in their intact environment. The possibility to observe single growth cones navigating their intermediate target allows for measuring growth speed, changes in morphology, or aberrant behavior. Moreover, observation of the intermediate target – the floor plate – revealed its active participation and interaction with commissural axons during midline crossing.Summary statementLive tracking of single growth cones is more informative about axonal behavior during navigation than inference of behavior from the analyses of snapshots of different growth cones.


2020 ◽  
Author(s):  
Saumya Jain ◽  
Ying Lin ◽  
Yerbol Kurmangaliyev ◽  
Parmis Mirshahidi ◽  
Brianna Parrington ◽  
...  

Wiring a complex brain relies on cell-type and temporal-specific expression of genes encoding cell recognition molecules regulating circuit formation1–3. Though genetic programs driving cell-type specificity have been described4–6, how precise temporal control is achieved remains unknown. Here, we describe a global program for the temporal regulation of cell-type-specific wiring genes in the Drosophila visual system. We show that the Ecdysone Receptor induces a synchronous cascade of transcription factors in neurons throughout the visual system in a highly stereotyped fashion. Single-cell RNA-seq analysis of neurons lacking transcription factors in the cascade revealed that targets are cell-type dependent and these are enriched for wiring genes. Knock-down of different transcription factors in this cascade led to defects in sequential steps in wiring. Taken together, this work identifies a synchronous, global program for temporal control of different sets of wiring genes in different neurons. We speculate that this global program coordinates development across cell types to choreograph specific steps in circuit assembly.


Development ◽  
2021 ◽  
Vol 148 (18) ◽  
Author(s):  
Cory J. Weaver ◽  
Fabienne E. Poulain

ABSTRACT Since the pioneering work of Ramón y Cajal, scientists have sought to unravel the complexities of axon development underlying neural circuit formation. Micrometer-scale axonal growth cones navigate to targets that are often centimeters away. To reach their targets, growth cones react to dynamic environmental cues that change in the order of seconds to days. Proper axon growth and guidance are essential to circuit formation, and progress in imaging has been integral to studying these processes. In particular, advances in high- and super-resolution microscopy provide the spatial and temporal resolution required for studying developing axons. In this Review, we describe how improved microscopy has revolutionized our understanding of axonal development. We discuss how novel technologies, specifically light-sheet and super-resolution microscopy, led to new discoveries at the cellular scale by imaging axon outgrowth and circuit wiring with extreme precision. We next examine how advanced microscopy broadened our understanding of the subcellular dynamics driving axon growth and guidance. We finally assess the current challenges that the field of axonal biology still faces for imaging axons, and examine how future technology could meet these needs.


2021 ◽  
Vol 9 (5) ◽  
pp. 1107
Author(s):  
Wonho Choi ◽  
Yoshihiro Yamaguchi ◽  
Ji-Young Park ◽  
Sang-Hyun Park ◽  
Hyeok-Won Lee ◽  
...  

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.


2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.


2019 ◽  
Vol 34 (4) ◽  
pp. 419-437 ◽  
Author(s):  
Roberto Rocco ◽  
Luciana Royer ◽  
Fábio Mariz Gonçalves

2004 ◽  
Vol 19 (5) ◽  
pp. 1217-1225 ◽  
Author(s):  
Katsushige Sato ◽  
Naohisa Miyakawa ◽  
Yoko Momose-Sato

BJPsych Open ◽  
2018 ◽  
Vol 4 (5) ◽  
pp. 317-323 ◽  
Author(s):  
Asako Mori ◽  
Yasumasa Okamoto ◽  
Go Okada ◽  
Koki Takagaki ◽  
Masahiro Takamura ◽  
...  

BackgroundBehavioural activation is an efficient treatment for depression and can improve intrinsic motivation. Previous studies have revealed that the frontostriatal circuit is involved in intrinsic motivation; however, there are no data on how behavioural activation affects the frontostriatal circuit.AimsWe aimed to investigate behavioural activation-related changes in the frontostriatal circuit.MethodFifty-nine individuals with subthreshold depression were randomly assigned to either the intervention or non-intervention group. The intervention group received five weekly behavioural activation sessions. The participants underwent functional magnetic resonance imaging scanning on two separate occasions while performing a stopwatch task based on intrinsic motivation. We investigated changes in neural activity and functional connectivity after behavioural activation.ResultsAfter behavioural activation, the intervention group had increased activation and connectivity in the frontostriatal region compared with the non-intervention group. The increased activation in the right middle frontal gyrus was correlated with an improvement of subjective sensitivity to environmental rewards.ConclusionsBehavioural activation-related changes to the frontostriatal circuit advance our understanding of psychotherapy-induced improvements in the neural basis of intrinsic motivation.Declaration of interestNone.


2013 ◽  
Vol 24 (3) ◽  
pp. 146-155 ◽  
Author(s):  
Marie-Laure Baudet ◽  
Anaïs Bellon ◽  
Christine E. Holt

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