scholarly journals Repairing neural damage in a C. elegans chemosensory circuit using genetically engineered synapses

2020 ◽  
Author(s):  
Ithai Rabinowitch ◽  
Bishal Upadhyaya ◽  
Aaradhya Pant ◽  
Jihong Bai
Keyword(s):  
Information Flow ◽  
Neural Circuit ◽  
Neuronal Loss ◽  
Genetically Engineered ◽  
Electrical Synapses ◽  
C Elegans ◽  
Normal Behavior ◽  
Successful Recovery ◽  
Circuit Function ◽  
Electrical Connections

AbstractNeuronal loss can considerably diminish neural circuit function, impairing normal behavior by disrupting information flow in the circuit. We reasoned that by rerouting the flow of information in the damaged circuit it may be possible to offset these negative outcomes. We examined this possibility using the well-characterized chemosensory circuit of the nematode worm C. elegans. In this circuit, a main sensory neuron class sends parallel outputs to several interneuron classes. We found that the removal of one of these interneuron classes impairs chemotaxis to attractive odors, revealing a prominent path for information flow in the circuit. To alleviate these deficiencies, we sought to reinforce a remaining neural pathway. We used genetically engineered electrical synapses for this purpose, and observed the successful recovery of chemotaxis performance. However, we were surprised to find that the recovery was largely mediated by inadvertently formed left-right lateral electrical connections within individual neuron classes. Our analysis suggests that these additional electrical synapses help restore circuit function by amplifying weakened neuronal signals in the damaged circuit. These results demonstrate the power of genetically engineered synapses to regulate information flow and signal intensity in damaged neural circuits.

scholarly journals MALT1 mediates IL-17 Neural Signaling to regulate C. elegans behavior, immunity and longevity

2019 ◽  
Author(s):  
Sean M. Flynn ◽  
Changchun Chen ◽  
Murat Artan ◽  
Stephen Barratt ◽  
Alastair Crisp ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Circuit ◽  
Escape Behavior ◽  
Interleukin 17 ◽  
Neural Function ◽  
Behavioral State ◽  
C Elegans ◽  
Nervous System Function ◽  
Circuit Function ◽  
Neural Signaling

AbstractBesides well-known immune roles, the evolutionarily ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate how IL-17 signals in neurons, and the extent to which this signaling can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans (Ce) neurons. We identify the Ce ortholog of MALT1 as a critical output of the pathway. MALT1 was not previously implicated in IL-17 signaling or in nervous system function. MALT1 forms a complex with homologs of Act1 and IRAK and functions both as a scaffold for IκB recruitment, and as a protease. MALT1 is expressed broadly in the Ce nervous system, and neuronal IL-17–MALT1 signaling regulates many phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural function downstream of IL-17 to remodel physiological and behavioral state.

scholarly journals PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans

2012 ◽  
Vol 15 (12) ◽  
pp. 1675-1682 ◽  
Author(s):  
Arantza Barrios ◽  
Rajarshi Ghosh ◽  
Chunhui Fang ◽  
Scott W Emmons ◽  
Maureen M Barr
Keyword(s):  
Neural Circuit ◽  
Searching Behavior ◽  
Mate Searching ◽  
C Elegans

scholarly journals Neural circuit function redundancy in brain disorders

2021 ◽  
Vol 70 ◽  
pp. 74-80
Author(s):  
Beatriz E.P. Mizusaki ◽  
Cian O'Donnell
Keyword(s):  
Neural Circuit ◽  
Brain Disorders ◽  
Circuit Function

scholarly journals Zebrafish Dscaml1 is Essential for Retinal Patterning and Function of Oculomotor Subcircuits

2019 ◽  
Author(s):  
Manxiu Ma ◽  
Alexandro D. Ramirez ◽  
Tong Wang ◽  
Rachel L. Roberts ◽  
Katherine E. Harmon ◽  
...  
Keyword(s):  
Animal Model ◽  
Light Adaptation ◽  
Neural Circuit ◽  
Oculomotor System ◽  
Gaze Stabilization ◽  
Ocular Disorders ◽  
Motor Apraxia ◽  
Premotor Pathways ◽  
And Function ◽  
Circuit Function

AbstractDown Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the role of dscaml1 in the zebrafish oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Loss of zebrafish dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses showed that mutants have abnormal gaze stabilization, impaired fixation, disconjugation, and faster fatigue. Notably, the saccade and fatigue phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, for which no animal model exists. Two-photon calcium imaging showed that loss of dscaml1 leads to impairment in the saccadic premotor pathway but not the pretectum-vestibular premotor pathway, indicating a subcircuit requirement for dscaml1. Together, we show that dscaml1 has both broad and specific roles in oculomotor circuit function, providing a new animal model to investigate the development of premotor pathways and their associated human ocular disorders.

scholarly journals Quantitative synapse analysis for cell-type specific connectomics

2018 ◽  
Author(s):  
Dika A. Kuljis ◽  
Khaled Zemoura ◽  
Cheryl A. Telmer ◽  
Jiseok Lee ◽  
Eunsol Park ◽  
...  
Keyword(s):  
Large Scale ◽  
Neural Circuit ◽  
Apical Dendrite ◽  
Automated Detection ◽  
Cell Type ◽  
Disease States ◽  
Specific Localization ◽  
Cell Type Specific ◽  
Dendritic Branches ◽  
Circuit Function

AbstractAnatomical methods for determining cell-type specific connectivity are essential to inspire and constrain our understanding of neural circuit function. We developed new genetically-encoded reagents for fluorescence-synapse labeling and connectivity analysis in brain tissue, using a fluorogen-activating protein (FAP)-or YFP-coupled, postsynaptically-localized neuroligin-1 targeting sequence (FAP/YFPpost). Sparse viral expression of FAP/YFPpost with the cell-filling, red fluorophore dTomato (dTom) enabled high-throughput, compartment-specific localization of synapses across diverse neuron types in mouse somatosensory cortex. High-resolution confocal image stacks of virally-transduced neurons were used for 3D reconstructions of postsynaptic cells and automated detection of synaptic puncta. We took advantage of the bright, far-red emission of FAPpost puncta for multichannel fluorescence alignment of dendrites, synapses, and presynaptic neurites to assess subtype-specific inhibitory connectivity onto L2 neocortical pyramidal (Pyr) neurons. Quantitative and compartment-specific comparisons show that PV inputs are the dominant source of inhibition at both the soma and across all dendritic branches examined and were particularly concentrated at the primary apical dendrite, a previously unrecognized compartment of L2 Pyr neurons. Our fluorescence-based synapse labeling reagents will facilitate large-scale and cell-type specific quantitation of changes in synaptic connectivity across development, learning, and disease states.

scholarly journals Rapid and sustained homeostatic control of presynaptic exocytosis at a central synapse

2019 ◽  
Vol 116 (47) ◽  
pp. 23783-23789 ◽  
Author(s):  
Igor Delvendahl ◽  
Katarzyna Kita ◽  
Martin Müller
Keyword(s):  
Time Scales ◽  
Neural Circuit ◽  
Mossy Fiber ◽  
Pool Size ◽  
Homeostatic Plasticity ◽  
Experimental Conditions ◽  
Central Synapse ◽  
Circuit Function ◽  
Vesicle Pool ◽  
Activity Dependent

Animal behavior is remarkably robust despite constant changes in neural activity. Homeostatic plasticity stabilizes central nervous system (CNS) function on time scales of hours to days. If and how CNS function is stabilized on more rapid time scales remains unknown. Here, we discovered that mossy fiber synapses in the mouse cerebellum homeostatically control synaptic efficacy within minutes after pharmacological glutamate receptor impairment. This rapid form of homeostatic plasticity is expressed presynaptically. We show that modulations of readily releasable vesicle pool size and release probability normalize synaptic strength in a hierarchical fashion upon acute pharmacological and prolonged genetic receptor perturbation. Presynaptic membrane capacitance measurements directly demonstrate regulation of vesicle pool size upon receptor impairment. Moreover, presynaptic voltage-clamp analysis revealed increased Ca2+-current density under specific experimental conditions. Thus, homeostatic modulation of presynaptic exocytosis through specific mechanisms stabilizes synaptic transmission in a CNS circuit on time scales ranging from minutes to months. Rapid presynaptic homeostatic plasticity may ensure stable neural circuit function in light of rapid activity-dependent plasticity.

Optogenetic Dissection of Neural Circuit Function in Behaving Animals

2014 ◽  
pp. 143-160
Author(s):  
Carolina Gutierrez Herrera ◽  
Antoine Adamantidis ◽  
Feng Zhang ◽  
Karl Deisseroth ◽  
Luis de Lecea
Keyword(s):  
Neural Circuit ◽  
Circuit Function

Live demonstration: Spiking neural circuit based navigation inspired by C. elegans thermotaxis

2015 ◽  
Author(s):  
Chirag Shetty ◽  
Sri Nitchith ◽  
Rishabh Rawat ◽  
S. R. Nandakumar ◽  
Pritesh Shah ◽  
...  
Keyword(s):  
Neural Circuit ◽  
C Elegans ◽  
Live Demonstration

scholarly journals Insulin-like signaling and the neural circuit for integrative behavior in C. elegans

2006 ◽  
Vol 20 (21) ◽  
pp. 2955-2960 ◽  
Author(s):  
E. Kodama ◽  
A. Kuhara ◽  
A. Mohri-Shiomi ◽  
K. D. Kimura ◽  
M. Okumura ◽  
...  
Keyword(s):  
Neural Circuit ◽  
C Elegans

A Dynamic Body Model of the NematodeC. eleganswith Neural Oscillators

2005 ◽  
Vol 17 (3) ◽  
pp. 318-326 ◽  
Author(s):  
Michiyo Suzuki ◽  
◽  
Takeshi Goto ◽  
Toshio Tsuji ◽  
Hisao Ohtake ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Motor Control ◽  
Caenorhabditis Elegans ◽  
Neural Circuit ◽  
Rhythmic Movement ◽  
Circuit Model ◽  
Neural Oscillators ◽  
C Elegans ◽  
Body Model ◽  
Multicellular Organisms

The nematode <I>Caenorhabditis elegans (C. elegans)</I>, a relatively simple organism in structure, is one of the most well-studied multicellular organisms. We developed a <I>virtual C. elegans</I> based on the actual organism to analyze motor control. We propose a dynamic body model, including muscles, controlled by a neural circuit model based on the actual nematode. The model uses neural oscillators to generate rhythmic movement. Computer simulation confirmed that the <I>virtual C. elegans</I> realizes motor control similar qualitatively to that of the actual organism. Specified classes of neurons are killed in the neural circuit model corresponding to actual <I>unc</I> mutants, demonstrating that resulting movement of the <I>virtual C. elegans</I> resembles that of actual mutants.

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