scholarly journals Molecular mechanisms regulating synaptic specificity and retinal circuit formation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hannah K. Graham ◽  
Xin Duan
Keyword(s):  
Molecular Mechanisms ◽  
Synaptic Specificity ◽  
Circuit Formation

scholarly journals Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation

2021 ◽  
Author(s):  
Mai Ahmed ◽  
Yutaka Kojima ◽  
Ichiro Masai
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Interacting Protein ◽  
Retina Development ◽  
Circuit Formation

In the vertebrate retina, an interplay between retinal ganglion cells (RGCs), amacrine and bipolar cells establishes a synaptic layer called the inner plexiform layer (IPL). This circuit conveys signals from photoreceptors to visual centers in the brain. However, the molecular mechanisms involved in its development remain poorly understood. Striatin-interacting protein 1 (Strip1) is a core component of the STRIPAK complex, and it has shown emerging roles in embryonic morphogenesis. Here, we uncover the importance of Strip1 in inner retina development. Using zebrafish, we show that loss of Strip1 causes defects in IPL formation. In strip1 mutants, RGCs undergo dramatic cell death shortly after birth. Amacrine and bipolar cells subsequently invade the degenerating RGC layer, leading to a disorganized IPL. Thus, Strip1 promotes IPL formation through RGC maintenance. Mechanistically, zebrafish Strip1 interacts with its STRIPAK partner, Striatin3, to promote RGC survival by suppressing Jun-mediated apoptosis. In addition to its function in RGC maintenance, Strip1 is required for RGC dendritic patterning, which likely contributes to proper IPL formation. Taken together, we propose that a series of Strip1-mediated regulatory events coordinates inner retinal circuit formation by maintaining RGCs during development, which ensures proper positioning and neurite patterning of inner retinal neurons.

scholarly journals Molecular mechanisms of synaptic specificity

2010 ◽  
Vol 43 (3) ◽  
pp. 261-267 ◽  
Author(s):  
Milica A. Margeta ◽  
Kang Shen
Keyword(s):  
Molecular Mechanisms ◽  
Synaptic Specificity

scholarly journals CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4

2019 ◽  
Author(s):  
Andrew M. Garrett ◽  
Peter J. Bosch ◽  
David M. Steffen ◽  
Leah C. Fuller ◽  
Charles G. Marcucci ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Neuronal Survival ◽  
Allelic Series ◽  
Isoform Diversity ◽  
Variable Exon ◽  
Human Orthologue ◽  
Mutant Lines ◽  
Circuit Formation

ABSTRACTThe mammalian Pcdhg gene cluster encodes a family of 22 cell adhesion molecules, the gamma-Protocadherins (γ-Pcdhs), critical for neuronal survival and neural circuit formation. The extent to which isoform diversity–aγ-Pcdh hallmark–is required for their functions remains unclear. We used a CRISPR/Cas9 approach to reduce isoform diversity, targeting each Pcdhg variable exon with pooled sgRNAs to generate an allelic series of 26 mouse lines with 1 to 21 isoforms disrupted via discrete indels at guide sites and/or larger deletions/rearrangements. Analysis of 5 mutant lines indicates that postnatal viability and neuronal survival do not require isoform diversity. Surprisingly, as it is the only γ-Pcdh that cannot independently engage in homophilic trans-interactions, we find that γC4, encoded by Pcdhgc4, is the only critical isoform. Because the human orthologue is the only PCDHG gene constrained in humans, our results indicate a conserved γC4 function that likely involves distinct molecular mechanisms.

scholarly journals Molecular mechanisms underlying neural circuit formation

2009 ◽  
Vol 19 (2) ◽  
pp. 162-167 ◽  
Author(s):  
Bai Lu ◽  
Kuan Hong Wang ◽  
Akinao Nose
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Circuit Formation

scholarly journals Evolutionary conservation of mechanisms for neural regionalization, proliferation and interconnection in brain development

2008 ◽  
Vol 5 (1) ◽  
pp. 112-116 ◽  
Author(s):  
Heinrich Reichert
Keyword(s):  
Brain Development ◽  
Molecular Mechanisms ◽  
Evolutionary Conservation ◽  
Model Systems ◽  
Embryonic Patterning ◽  
Developmental Control ◽  
Central Nervous Systems ◽  
Invertebrate Model ◽  
Circuit Formation ◽  
The Brain

Comparative studies of brain development in vertebrate and invertebrate model systems demonstrate remarkable similarities in expression and action of developmental control genes during embryonic patterning, neural proliferation and circuit formation in the brain. Thus, comparable sets of developmental control genes are involved in specifying the early brain primordium as well as in regionalized patterning along its anteroposterior and dorsoventral axes. Furthermore, similar cellular and molecular mechanisms underlie the formation and proliferation of neural stem cell-like progenitors that generate the neurons in the central nervous systems. Finally, neural identity and some complex circuit interconnections in specific brain domains appear to be comparable in vertebrates and invertebrates and may depend on similar developmental control genes.

scholarly journals Molecular Mechanisms of Synaptic Specificity in Developing Neural Circuits

Neuron ◽  
2010 ◽  
Vol 68 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Megan E. Williams ◽  
Joris de Wit ◽  
Anirvan Ghosh
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Synaptic Specificity

scholarly journals Autophagy is required for midbrain dopaminergic axon development and their responsiveness to guidance cues

2020 ◽  
Author(s):  
M.S. Profes ◽  
A. Saghatelyan ◽  
M. Lévesque
Keyword(s):  
Molecular Mechanisms ◽  
Axon Growth ◽  
Brain Functions ◽  
Guidance Cues ◽  
Axon Development ◽  
Wide Range ◽  
Growth Guidance ◽  
Circuit Formation

AbstractMesodiencephalic dopamine (mDA) neurons play a wide range of brain functions. Distinct subtypes of mDA neurons regulate these functions but the molecular mechanisms that drive the mDA circuit formation are largely unknown. Here we show that autophagy, the main recycling cellular pathway, is present in the growth cones of developing mDA neurons and its level changes dynamically in response to guidance cues. To characterize the role of autophagy in mDA axon growth/guidance, we knocked-out (KO) essential autophagy genes (Atg12, Atg5) in mice mDA neurons. Autophagy deficient mDA axons exhibit axonal swellings and decreased branching both in vitro and in vivo, likely due to aberrant microtubule looping. Strikingly, deletion of autophagy-related genes, blunted completely the response of mDA neurons to chemo-repulsive and chemo-attractive guidance cues. Our data demonstrate that autophagy plays a central role in regulating mDA neurons development, orchestrating axonal growth and guidance.

scholarly journals In VitroStudies of Neuronal Networks and Synaptic Plasticity in Invertebrates and in Mammals Using Multielectrode Arrays

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Paolo Massobrio ◽  
Jacopo Tessadori ◽  
Michela Chiappalone ◽  
Mirella Ghirardi
Keyword(s):  
Neuronal Networks ◽  
Microelectrode Array ◽  
Molecular Mechanisms ◽  
Multielectrode Arrays ◽  
Neural Connections ◽  
Brain Functions ◽  
Array Technology ◽  
Circuit Formation

Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networksin vivoandin vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such asLymnaea,Aplysia, andHelix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments.

scholarly journals Axon guidance at the midline – a live imaging perspective

2020 ◽  
Author(s):  
Alexandre Dumoulin ◽  
Nikole R. Zuñiga ◽  
Esther T. Stoeckli
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Surface Expression ◽  
Growth Cones ◽  
Live Imaging ◽  
Growth Speed ◽  
Intermediate Target ◽  
Commissural Axons ◽  
Circuit Formation

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.

scholarly journals Architects in neural circuit design: Glia control neuron numbers and connectivity

2013 ◽  
Vol 203 (3) ◽  
pp. 395-405 ◽  
Author(s):  
Megan M. Corty ◽  
Marc R. Freeman
Keyword(s):  
Nervous System ◽  
Circuit Design ◽  
Glial Cells ◽  
Neural Development ◽  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Neuronal Circuit ◽  
Circuit Formation

Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron–glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

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