scholarly journals Connectomes across development reveal principles of brain maturation in C. elegans

Author(s):  
Daniel Witvliet ◽  
Ben Mulcahy ◽  
James K. Mitchell ◽  
Yaron Meirovitch ◽  
Daniel R. Berger ◽  
...  

AbstractFrom birth to adulthood, an animal’s nervous system changes as its body grows and its behaviours mature. However, the extent of circuit remodelling across the connectome is poorly understood. Here, we used serial-section electron microscopy to reconstruct the brain of eight isogenic C. elegans individuals at different ages to learn how an entire wiring diagram changes with maturation. We found that the overall geometry of the nervous system is preserved from birth to adulthood, establishing a constant scaffold upon which synaptic change is built. We observed substantial connectivity differences among individuals that make each brain partly unique. We also observed developmental connectivity changes that are consistent between animals but different among neurons, altering the strengths of existing connections and creating additional connections. Collective synaptic changes alter information processing of the brain. Across maturation, the decision-making circuitry is maintained whereas sensory and motor pathways are substantially remodelled, and the brain becomes progressively more modular and feedforward. These synaptic changes reveal principles that underlie brain maturation.

Author(s):  
Cornelia I. Bargmann

A wiring diagram of the Caenorhabditis elegans nervous system was constructed from serial-section electron micrographs 30 years ago. This wiring diagram divides the 302 neurons in the nervous system of the adult hermaphrodite into three overall classes: sensory neurons, motor neurons that form neuromuscular junctions, and interneurons that connect sensory neurons with motor neurons. Most sensory neurons and interneurons belong to bilaterally symmetric pairs with similar connections and morphologies, while motor neurons belong to larger classes. The C. elegans nervous system presents an exceptional situation in which neuroanatomical connections are extremely well defined and reproducible among animals. These detailed anatomical studies and a parallel genetic attack have increasingly been joined by functional and electrophysiological characterization.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Inna V Nechipurenko ◽  
Cristina Berciu ◽  
Piali Sengupta ◽  
Daniela Nicastro

The primary cilium is nucleated by the mother centriole-derived basal body (BB) via as yet poorly characterized mechanisms. BBs have been reported to degenerate following ciliogenesis in the C. elegans embryo, although neither BB architecture nor early ciliogenesis steps have been described in this organism. In a previous study (Doroquez et al., 2014), we described the three-dimensional morphologies of sensory neuron cilia in adult C. elegans hermaphrodites at high resolution. Here, we use serial section electron microscopy and tomography of staged C. elegans embryos to demonstrate that BBs remodel to support ciliogenesis in a subset of sensory neurons. We show that centriolar singlet microtubules are converted into BB doublets which subsequently grow asynchronously to template the ciliary axoneme, visualize degeneration of the centriole core, and define the developmental stage at which the transition zone is established. Our work provides a framework for future investigations into the mechanisms underlying BB remodeling.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
W Christopher Risher ◽  
Sagar Patel ◽  
Il Hwan Kim ◽  
Akiyoshi Uezu ◽  
Srishti Bhagat ◽  
...  

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.


2020 ◽  
Author(s):  
Zhikai Liu ◽  
Yukiko Kimura ◽  
Shin-ichi Higashijima ◽  
David G. Hildebrand ◽  
Joshua L. Morgan ◽  
...  

AbstractAs sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict this complexity is due to convergent inputs from neurons with diverse response properties, in most vertebrate systems convergence has only been inferred rather than tested directly. Here we measure sensory computations in zebrafish vestibular neurons across multiple axes in vivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. An independent approach, serial section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Our data also resolve a long-standing contradiction between anatomical and physiological analyses by revealing that sensory responses are produced by sparse but powerful inputs from vestibular afferents. Together these results provide a direct, quantifiable demonstration of feedforward input convergence in vivo.


Author(s):  
Vladislav Susoy ◽  
Wesley Hung ◽  
Daniel Witvliet ◽  
Joshua E. Whitener ◽  
Min Wu ◽  
...  

AbstractNatural goal-directed behaviors often involve complex sequences of many stimulus-triggered components. Understanding how brain circuits organize such behaviors requires mapping the interactions between an animal, its environment, and its nervous system. Here, we use continuous brain-wide neuronal imaging to study the full performance of mating by the C. elegans male. We show that as each mating unfolds in its own sequence of component behaviors, the brain operates similarly between instances of each component, but distinctly between different components. When the full sensory and behavioral context is taken into account, unique roles emerge for each neuron. Functional correlations between neurons are not fixed, but change with behavioral dynamics. From the contribution of individual neurons to circuits, our study shows how diverse brain-wide dynamics emerge from the integration of sensory perception and motor actions within their natural context.


2021 ◽  
Author(s):  
Tessa Tekieli ◽  
Eviatar Yemini ◽  
Amin Nejatbakhsh ◽  
Erdem Varol ◽  
Robert W Fernandez ◽  
...  

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode C. elegans. While 294 neurons are shared between the two sexes, the nervous system of the male contains an additional 93 male-specific neurons, most of which have received very little attention so far. To make these neurons amenable for future study, we describe here how a multicolor, multipromoter reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used this tool to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes. We demonstrate the usage of NeuroPAL for cellular fate analysis by analyzing the effect of removal of developmental patterning genes, including a HOX cluster gene (egl-5), a miRNA (lin-4) and a proneural gene (lin-32/Ato), on neuronal identity acquisition within the male-specific nervous system. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage that is concomitant with male tale retraction. This wave of differentiation couples neuronal maturation programs with the appearance of sexual organs. We call this wave 'just-in-time' differentiation by its analogy to the mechanism of 'just-in-time' transcription of metabolic pathway genes.


2021 ◽  
Vol 9 ◽  
Author(s):  
Matthew Cobb

Metaphors have formed a significant part of the development of neuroscience, often linked with technology. A metaphor that has been widely used for the past two centuries is that of the nervous system being like wires, either as a telegraph system or telephone exchange, or, more recently, in the more abstract metaphor of a wiring diagram. The entry of these terms into scientific writing is traced, together with the insights provided by these metaphors, in particular in relation to recent developments in the study of connectomes. Finally, the place of the wiring diagram as a modern version of Leibniz’s “mill” argument is described, as a way of exploring the limits of what insight the metaphor can provide


1929 ◽  
Vol 25 (2) ◽  
pp. 187-192
Author(s):  
M. A. Khazanov

The works of Zenker'a, Virchow'a, Stubli, Munk, Thager, Brown and others have adequately described the symptomatology, etiology, pathology and hemogram of trichinosis in humans. Comparatively, little attention was paid only to the phenomena of damage to the nervous system. Most of the authors are inclined to attribute a number of symptoms, such as the absence of tendon reflexes, electrical excitability disorder, Kernig's symptom, etc., due to exceptional muscle damage. Even severe cases of trichinosis with cerebral phenomena are interpreted by many authors (Trounner, Flurу, Nonne and Noerfner, etc.) as phenomena of a secondary order caused by the influence of toxic products. Meanwhile, the latest research by Gamrer and Gruber proved the presence of juvenile Trichinella in the meninges. In the cranial cavity under the dura mater they found copious amounts of fluid in which numerous juvenile Trichinella were found; they were also found in the pia mater and brain tissue. These data show that the nervous system is directly exposed to the invasion of Trichinella and a number of clinical phenomena are due exclusively to the damage to the nervous system. Already Stubli, in his classic monograph on trichinosis, cites 2 cases in which meningeal phenomena prevailed at the onset of the disease, and which, in his opinion, were caused by "acute cerebral edema or hydrocephalus". His in some of his cases of trichinosis observed clonus of the foot and Babinsky's symptom. Matthes believes that the excruciating headaches, paresthesia and neuralgia of trichinosis depend on the damage to the nervous system. Decastello notes that the absence of tendon reflexes is due to a violation of the motor pathways of the nerve, system. The opinion of these authors is confirmed by the data of pathological and anatomical studies. Knorr found small meningo-encephalitic foci during the autopsy of one case of trichinosis, although the patient had no meningitis during her lifetime. Gamper and Gruber also found numerous degenerative and proliferative foci in the brain and membranes in one patient who died of trichinosis.


2012 ◽  
Vol 18 (S2) ◽  
pp. 538-539
Author(s):  
C. Berciu ◽  
D. Nicastro ◽  
D.B. Doroquez ◽  
P. Sengupta

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.


Development ◽  
2021 ◽  
Author(s):  
Tessa Tekieli ◽  
Eviatar Yemini ◽  
Amin Nejatbakhsh ◽  
Chen Wang ◽  
Erdem Varol ◽  
...  

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode C. elegans, where male animals contain a little studied set of 93 male-specific neurons. To make these neurons amenable for future study, we describe here how a multicolor reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used NeuroPAL to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes and for cellular fate analysis by analyzing the effect of removal of several developmental patterning genes on neuronal identity acquisition. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage. This coordinated wave of differentiation, which we call “just-in-time" differentiation, couples neuronal maturation programs with the appearance of sexual organs.


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