Network Functions and Plasticity

Perspectives from Studying Neuronal Electrical Coupling in Microcircuits

Jian Jing

• Publisher: Academic Press
• Year: 2017
• Print ISBN: 9780128034712
• eBook ISBN: 9780128034996
• Topic: Medizin
• Subtopic: Neurologie

Network Functions and Plasticity: Perspectives from Studying Neuronal Electrical Coupling in Microcircuits focuses on the specific roles of electrical coupling in tractable, well-defined circuits, highlighting current research that offers novel insights for electrical coupling's roles in sensory and motor functions, neural computations, decision-making, regulation of network activity, circuit development, and learning and memory.Bringing together a diverse group of international experts and their contributions using a variety of approaches to study different invertebrate and vertebrate model systems with a focus on the role of electrical coupling/gap junctions in microcircuits, this book presents a timely contribution for students and researchers alike.- Provides an easy-to-read introduction on neural circuits of the model system- Focuses on the specific roles of electrical coupling in tractable, well-defined circuits- Includes recent discoveries and findings that are presented in the context of historical background- Outlines outstanding issues and future research in the field

Chapter 1

Electrical Coupling in Caenorhabditis elegans Mechanosensory Circuits

I. Rabinowitch¹, and W.R. Schafer^{2 1}Fred Hutchinson Cancer Research Center, Seattle, WA, United States ²MRC Laboratory of Molecular Biology, Cambridge, United Kingdom

Abstract

Electrical synapses formed by gap junctions are widespread in the human brain as well as in simpler nervous systems. The nematode Caenorhabditis elegans, with its completely mapped connectome of 302 neurons and approximately 4000 electrical synapses, is therefore well suited to investigate the functional importance of electrical coupling in neuronal microcircuits. We have found that hub-and-spoke gap junction circuit in C. elegans mediates the integration of mechanosensory information to control nose touch avoidance behavior. A combination of lateral facilitation between active inputs and inhibitory shunting to inactive inputs implements an analog coincidence detector, a property that might be shared with other hub-and-spoke circuits. We also describe transgenic methods for the synthetic insertion of ectopic gap junctions, which may have broad experimental applications.

Keywords

C. elegans; Hub and spoke; Innexin; Mechanosensation

1. Introduction

The nematode Caenorhabditis elegans is in many ways an ideal organism to investigate microcircuits and their roles in behavior. It is currently the only organism with a complete physical connectome; each of its 302 neurons has been individually identified and its synaptic and gap junctional connections mapped at the level of electron microscopy. It is also highly accessible to genetic manipulation, with a sequenced genome, a short generation time, and amenability to transgenesis and gene replacement. Moreover, its transparency and compactness have made it well suited for optogenetic manipulation and recording of neural activity in behaving animals. Together, these tools make it possible to dissect how the interactions between defined neurons generate the functional properties of microcircuits, and how those properties relate to whole animal behavior.

Gap junctions form an important component of the C. elegans connectome. The published C. elegans “wiring diagram” includes approximately 900 gap junctions along with 8000 chemical synapses (White et al., 1986). Analyses using modern machine vision methods (Xu et al., 2013) suggest this is an underestimate, with over 4000 gap junctions reported in data published online (wormwiring.org). Like other invertebrates, C. elegans gap junctions are formed from innexins rather than connexins (Altun et al., 2009; Simonsen et al., 2014). The C. elegans genome contains 25 innexin genes, 20 of which are neuronally expressed (Altun et al., 2009). These show varying patterns of expression, some expressed widely and others in only a few neurons. A few have been shown to have behavioral phenotypes; for example, loss-of-function mutations in unc-7 and unc-9, which are expressed in motorneurons and premotor interneurons, result in strongly uncoordinated movement (Kawano et al., 2011).

The pattern of gap junction connections in the worm nervous system has been analyzed with the goal of identifying motifs of potential functional importance. In particular, the frequencies of all possible three-neuron and four-neuron connectivity patterns have been determined and compared with their expected frequencies in a random network (Varshney et al., 2011). Overrepresented patterns, such as a triangular connection of three neurons, might represent microcircuit elements with a conserved function in computation. One overrepresented motif observed in the four-neuron analysis is the hub and spoke, in which a single hub neuron is connected to each of the other three neurons (“spokes”). Another overrepresented four-neuron motif is the “diamond” motif whereby all neuron pairs except for one are connected by gap junctions (Varshney et al., 2011). The hub-and-spoke architecture, whereby multiple neurons are connected to one central neuron, is a recurring circuit motif in the C. elegans connectome (Varshney et al., 2011); indeed, larger hub-and-spoke circuits, with a single hub receiving gap junctions from a large number of “spoke” inputs, are not uncommon. For example, the hub-and-spoke circuit in which many sensory neurons of varying modalities are connected by gap junctions to interneurons called RMG has been shown to control aggregation behavior, and to modulate responses to nematode pheromones (Macosko et al., 2009; Jang et al., 2012).

We have undertaken an analysis of a simpler hub-and-spoke network involved in nose touch (Chatzigeorgiou and Schafer, 2011; Rabinowitch et al., 2013). This circuit involves a small number of input neurons of a single (mechanosensory) modality, and the behavioral output, an escape response called a reversal, is robust and easily correlated with the activity of the hub neuron. From these studies, we have aimed to uncover general principles of how hub-and-spoke circuits process information and control behavior.

2. The Nose Touch Circuit

The natural habitat of C. elegans consists of soil and rotting fruit. With no sense of vision, it relies heavily on a range of mechanosensory cues to navigate, locate food, interact with conspecifics, and avoid threats. Such complex interaction with the environment presents several challenges to the worm's mechanosensory system. It must be able to discriminate between different textures and patterns, distinguishing, for example, between food (bacteria), soil particles, a mating partner, and a predator. In addition, its dynamic range must be extensive enough to detect both the gentlest and harshest mechanical inputs. Gap junctions might be useful building blocks for neural circuits that implement these features. We demonstrate this in the nose touch circuit, one of several neural circuits involved in mechanosensation in C. elegans. Other circuits include the polymodal nociceptive circuit involving the ASH neurons (Kaplan and Horvitz, 1993; Hart et al., 1995), the gentle body touch circuit (Chalfie et al., 1985), and the harsh body touch circuit (Way and Chalfie, 1989).

The nose touch circuit is important for the transduction and processing of mechanosensory information sensed by the nose, often the first body part to come into contact with the changing texture that the worm encounters as it navigates through its surroundings. The circuit comprises several classes of mechanosensory neurons. The neurons in each class share a distinct morphology, are equipped with specific mechanoreceptors, and are linked to separate downstream circuits (Fig. 1.1): Four CEP neurons extend their dendrites to the tip of the nose and require the transient receptor potential N channel TRP-4 for mechanosensory transduction (Li et al., 2006; Kindt et al., 2007a; Kang et al., 2010). These neurons are dopaminergic and are involved in modifying locomotion on physical contact with food (Sawin et al., 2000). Four OLQ neurons have similar morphology to the CEPs. However, they use different mechanoreceptors, the transient receptor potential V channel OSM-9 (Colbert et al., 1997; Chatzigeorgiou and Schafer, 2011), and the transient receptor potential A (TRPA) channel TRPA-1 (Kindt et al., 2007b). These neurons are involved in controlling foraging and head withdrawal. Two FLP neurons have multidendritic processes. This is a rare morphology for C. elegans neurons, most of which have a simple bipolar structure. They use the degenerin/epithelial-like sodium channel (DEG/ENaC) channel MEC-10 to detect both gentle and harsh mechanical contact with the nose (Huang and Chalfie, 1994; Chatzigeorgiou and Schafer, 2011). The FLP neurons form part of an escape mechanism responsive to noxious physical stimulation of the nose.

Figure 1.1 The C. elegans nose touch circuit.

The C. elegans nose touch circuit consists of the CEP, OLQ, and FLP mechanosensory neurons (rectangles), each expressing specific mec...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• List of Contributors
• Preface
• Chapter 1. Electrical Coupling in Caenorhabditis elegans Mechanosensory Circuits
• Chapter 2. Neural Circuits Underlying Escape Behavior in Drosophila: Focus on Electrical Signaling
• Chapter 3. Gap Junctions Underlying Labile Memory
• Chapter 4. The Role of Electrical Coupling in Rhythm Generation in Small Networks
• Chapter 5. Network Functions of Electrical Coupling Present in Multiple and Specific Sites in Behavior-Generating Circuits
• Chapter 6. Electrical Synapses and Learning–Induced Plasticity in Motor Rhythmogenesis
• Chapter 7. Electrical Synapses and Neuroendocrine Cell Function
• Chapter 8. Electrical Synapses in Fishes: Their Relevance to Synaptic Transmission
• Chapter 9. Dynamic Properties of Electrically Coupled Retinal Networks
• Chapter 10. Circadian and Light-Adaptive Control of Electrical Synaptic Plasticity in the Vertebrate Retina
• Chapter 11. Electrical Coupling in the Generation of Vertebrate Motor Rhythms
• Chapter 12. Implications of Electrical Synapse Plasticity in the Inferior Olive
• Chapter 13. Gap Junctions Between Pyramidal Cells Account for a Variety of Very Fast Network Oscillations (>80Hz) in Cortical Structures
• Chapter 14. Lineage-Dependent Electrical Synapse Formation in the Mammalian Neocortex
• Glossary
• Index