Building stereotypic connectivity: mechanistic insights into structural plasticity from C. elegans

Abstract

The ability of neurons to modify or remodel their synaptic connectivity is critical for the function of neural circuitry throughout the life of an animal. Understanding the mechanisms underlying neuronal structural changes is central to our knowledge of how the nervous system is shaped for complex behaviors and how it further adapts to developmental and environmental demands. Caenorhabditis elegans provides a powerful model for examining developmental processes and for discovering mechanisms controlling neural plasticity. Recent findings have identified conserved themes underlying neural plasticity in development and under environmental stress.

Figure 1. Synaptic rewiring of DD motor neurons in L1 stage

A. Illustration of position and morphology of six DD-type GABA motor neurons, which also shows remodeling of pre- and post-synaptic components. Synapses (red puncta) of DDs are localized on the ventral processes in L1 animals, but appear on dorsal processes in L2 and older animals, while the ventral juvenile synapses are eliminated. At L1, DDs receive input from DA/DB on the dorsal process, and innervate ventral muscles. Rewired DDs receive inputs from VA/VB ventrally, and innervate dorsal muscles from L2 to adult. B. Genetic regulation of DD synaptic rewiring. lin-14 activity is high at L1 and acts to repress DD rewiring. One downstream transcriptional target of lin-14, the Ig-domain containing factor oig-1, functions to maintain L1-connectivity of DDs. lin-14 activity is downregulated at the end of L1, and meanwhile myrf-1 and myrf-2 are both upregulated and promote DD rewiring. C. Full length MYRF-1 and MYRF-2 localize on the ER membrane in DDs. They form trimers on the ER and undergo cleavage, releasing N-terminal fragments. The N-MYRFs translocate into the nucleus and regulate synaptic rewiring.

Figure 2. Establishing sex-specific connectivity

Interneurons AVA, AVG, and sensory neuron PHB are common to both hermaphrodites (shown in the drawing) and males. PHB synapses onto both AVA and AVG in early larvae. During sex maturation, sex-specific synapse pruning occurs, producing sex-dimorphic connectivity. Illustration is based on Ref [43].

Figure 3. Structural plasticity in sensory neurons

A. IL2 neuron (red) extends one simple dendrite to the nose in non-dauer animals (upper left panel), while the IL2 of dauer extends high-order dendritic branches (lower left panel), and also generates a 1d° dendrite directed posteriorly from the cell body. Right: 3-D schematic of a transverse segment of a dauer animal showing IL2 dendritic branches. Illustration is redrawn from Ref [46]. B. In dauers, two amphid sheaths (red) at the left and right sides expand and fuse into each other. The cilia endings of AWC (green), wrapped inside the amphid sheath, also expand and become overlapped. Middle: sagittal section view. Right: cross section view of non-dauer and dauer animals, respectively. Illustration is redrawn from Ref [47].

Figure 4. Trans-differentiation in cell fate plasticity

A. In hermaphrodites, epithelial cell Y (brown) retracts from the rectum and migrates anteriodorsally, transdifferentiating into a PDA motor neuron. Another cell, P12.pa, replaces the Y cell at the rectum. The time line (bottom) denotes the stage of larval development when the transdifferentiation occurs. Illustration is redrawn from Ref [56]. B. Amphid socket cell (AMso), a fully differentiated glia cell, divides and gives rise to an interneuron MCM only in males during sex maturation in L4. The second daughter cell from the division remains an AMso glia cell. Illustration is redrawn from Ref [41].