Neurexin controls plasticity of a mature, sexually dimorphic neuron

During development and adulthood, brain plasticity is evident at several levels, from synaptic structure and function to the outgrowth of dendrites and axons. Whether and how sex impinges on neuronal plasticity is poorly understood. Here we show that the sex-shared GABA (γ-aminobutyric acid)-releasing DVB neuron in Caenorhabditis elegans displays experience-dependent and sexually dimorphic morphological plasticity, characterized by the stochastic and dynamic addition of multiple neurites in adult males. These added neurites enable synaptic rewiring of the DVB neuron and instruct a functional switch of the neuron that directly modifies a step of male mating behaviour. Both DVB neuron function and male mating behaviour can be altered by experience and by manipulation of postsynaptic activity. The outgrowth of DVB neurites is promoted by presynaptic neurexin and antagonized by postsynaptic neuroligin, revealing a non-conventional activity and mode of interaction of these conserved, human-disease-relevant factors.

[1]  Quan Yuan,et al.  Structural homeostasis in the nervous system: a balancing act for wiring plasticity and stability , 2015, Front. Cell. Neurosci..

[2]  Y. Goda,et al.  The interplay between Hebbian and homeostatic synaptic plasticity , 2013, The Journal of cell biology.

[3]  Travis A. Jarrell,et al.  The Connectome of a Decision-Making Neural Network , 2012, Science.

[4]  J. Sulston,et al.  The Caenorhabditis elegans male: postembryonic development of nongonadal structures. , 1980, Developmental biology.

[5]  G. Ruvkun,et al.  The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons. , 1999, Development.

[6]  B. LeBoeuf,et al.  Caenorhabditis elegans male sensory-motor neurons and dopaminergic support cells couple ejaculation and post-ejaculatory behaviors , 2014, eLife.

[7]  Erik M. Jorgensen,et al.  The Sensory Circuitry for Sexual Attraction in C. elegans Males , 2007, Current Biology.

[8]  Aravinthan D. T. Samuel,et al.  Laser microsurgery in Caenorhabditis elegans. , 2012, Methods in cell biology.

[9]  B. LeBoeuf,et al.  Caenorhabditis elegans Male Copulation Circuitry Incorporates Sex-Shared Defecation Components To Promote Intromission and Sperm Transfer , 2016, G3: Genes, Genomes, Genetics.

[10]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[11]  Tobias Bonhoeffer,et al.  Loss of Sensory Input Causes Rapid Structural Changes of Inhibitory Neurons in Adult Mouse Visual Cortex , 2011, Neuron.

[12]  D. Hall,et al.  The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway , 2001, Current Biology.

[13]  Gary Ruvkun,et al.  A Conserved LIM Protein That Affects Muscular Adherens Junction Integrity and Mechanosensory Function in Caenorhabditis elegans , 1999, The Journal of cell biology.

[14]  Hollis G. Potter,et al.  Author Manuscript , 2013 .

[15]  P. Sternberg,et al.  Caenorhabditis elegans UNC-103 ERG-Like Potassium Channel Regulates Contractile Behaviors of Sex Muscles in Males before and during Mating , 2003, The Journal of Neuroscience.

[16]  M. Zhen,et al.  MADD-4/Punctin and Neurexin Organize C. elegans GABAergic Postsynapses through Neuroligin , 2015, Neuron.

[17]  Kyunghwa Lee,et al.  Neural Sex Modifies the Function of a C. elegans Sensory Circuit , 2007, Current Biology.

[18]  A. Gordus,et al.  Inducible and titratable silencing of Caenorhabditis elegans neurons in vivo with histamine-gated chloride channels , 2014, Proceedings of the National Academy of Sciences.

[19]  B. LeBoeuf,et al.  C. elegans Dopaminergic D2-Like Receptors Delimit Recurrent Cholinergic-Mediated Motor Programs during a Goal-Oriented Behavior , 2012, PLoS genetics.

[20]  Y. Zuo,et al.  Experience-dependent structural plasticity in the cortex , 2011, Trends in Neurosciences.

[21]  Emily A. Bayer,et al.  Sex-specific pruning of neuronal synapses in Caenorhabditis elegans , 2016, Nature.

[22]  P. Sternberg,et al.  Regulation of Distinct Muscle Behaviors Controls the C. elegans Male's Copulatory Spicules during Mating , 2001, Cell.

[23]  D. Reiner,et al.  Reversal of a muscle response to GABA during C. elegans male development , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  B. LeBoeuf,et al.  Gαq-Coupled Muscarinic Acetylcholine Receptors Enhance Nicotinic Acetylcholine Receptor Signaling in Caenorhabditis elegans Mating Behavior , 2007, The Journal of Neuroscience.

[25]  C. Gilbert,et al.  Large-Scale Axonal Reorganization of Inhibitory Neurons following Retinal Lesions , 2014, The Journal of Neuroscience.

[26]  K. Wȩdzony,et al.  Neuroligins, synapse balance and neuropsychiatric disorders , 2014, Pharmacological reports : PR.

[27]  O. Hobert,et al.  The neurexin superfamily of Caenorhabditis elegans. , 2011, Gene expression patterns : GEP.

[28]  K. Svoboda,et al.  Experience-dependent structural synaptic plasticity in the mammalian brain , 2009, Nature Reviews Neuroscience.

[29]  D. G. Gualberto,et al.  Behavioral decay in aging male C. elegans correlates with increased cell excitability , 2012, Neurobiology of Aging.

[30]  B. LeBoeuf,et al.  Diversity in Mating Behavior of Hermaphroditic and Male–Female Caenorhabditis Nematodes , 2007, Genetics.

[31]  J. Douglas Armstrong,et al.  Bioinformatics Applications Note Systems Biology Simple Neurite Tracer: Open Source Software for Reconstruction, Visualization and Analysis of Neuronal Processes , 2022 .

[32]  P. Scheiffele,et al.  Control of Excitatory and Inhibitory Synapse Formation by Neuroligins , 2005, Science.

[33]  R. Lints,et al.  A Cholinergic-Regulated Circuit Coordinates the Maintenance and Bi-Stable States of a Sensory-Motor Behavior during Caenorhabditis elegans Male Copulation , 2011, PLoS genetics.

[34]  E. Jorgensen,et al.  Spillover Transmission Is Mediated by the Excitatory GABA Receptor LGC-35 in C. elegans , 2015, The Journal of Neuroscience.

[35]  Enrico Cherubini,et al.  Alterations of GABAergic Signaling in Autism Spectrum Disorders , 2011, Neural plasticity.

[36]  Douglas S. Portman,et al.  Distributed Effects of Biological Sex Define Sex-Typical Motor Behavior in Caenorhabditis elegans , 2014, The Journal of Neuroscience.

[37]  M. Bang,et al.  A Matter of Balance: Role of Neurexin and Neuroligin at the Synapse , 2013, Neurochemical Research.

[38]  B. LeBoeuf,et al.  Cell Excitability Necessary for Male Mating Behavior in Caenorhabditis elegans Is Coordinated by Interactions Between Big Current and Ether-A-Go-Go Family K+ Channels , 2012, Genetics.

[39]  Cori Bargmann,et al.  GFP Reconstitution Across Synaptic Partners (GRASP) Defines Cell Contacts and Synapses in Living Nervous Systems , 2008, Neuron.

[40]  G. Feng,et al.  Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex , 2005, PLoS biology.

[41]  Cori Bargmann,et al.  C. elegans Responds to Chemical Repellents by Integrating Sensory Inputs from the Head and the Tail , 2002, Current Biology.