Plasticity of the electrical connectome ofC. elegans

Abstract

The patterns of electrical synapses of an animal nervous system ("electrical connectome"), as well as the functional properties and plasticity of electrical synapses, are defined by the neuron type-specific complement of electrical synapse constituents. We systematically examine here properties of the electrical connectome of the nematode C. elegans through a genome-and nervous system-wide analysis of the expression pattern of the central components of invertebrate electrical synapses, the innexins, revealing highly complex combinatorial patterns of innexin expression throughout the nervous system. We find that the complex expression patterns of 12 out of 14 neuronally expressed innexins change in a strikingly neuron type-specific manner throughout most of the nervous system, if animals encounter harsh environmental conditions and enter the dauer arrest stage. We systematically describe the plasticity of locomotory patterns of dauer stage animals and, by analyzing several individual electrical synapses, we demonstrate that dauer stage-specific electrical synapse remodeling is responsible for specific aspects of the altered locomotory patterns as well as altered chemosensory behavior of dauer stage animals. We describe an intersectional gene regulatory mechanism, involving terminal selector and FoxO transcription factors that are responsible for inducing innexin expression changes in a neuron type-and environment-specific manner. Taken together, our studies illustrate the remarkably dynamic nature of electrical synapses on a nervous system-wide level and describe regulatory strategies for how these alterations are achieved.

Brn3/POU‐IV‐type POU homeobox genes—Paradigmatic regulators of neuronal identity across phylogeny

“…See text for references. A number of innexin genes are also turned on or off in unc‐86 ‐dependent neuron classes upon entry into the dauer stage (Bhattacharya, Aghayeva, Berghoff, & Hobert, ). It is not presently clear if and how unc‐86 and dauer‐specific TFs, such as DAF‐16/FoxO are involved in controlling dynamic innexin expression, but one possibility is that in analogy to the sex‐specific cases, DAF‐16/FoxO may promote or antagonize the activity of UNC‐86 on innexin target genes.…”

“…This remodeling requires unc‐86 function (Schroeder et al, ). During entry into the dauer stage many other features of the nervous system become remodeled, including many of the electrical synapses throughout the entire nervous system, as assessed by changes in the expression of innexin genes (Bhattacharya et al, ). Innexin expression changes occur in many neurons that have been genetically specified by unc‐86 but whether unc‐86 is involved in controlling these changes as well is not presently known.…”

“…The cases mentioned above illustrate that while unc‐86 is apparently required to permit certain neuronal properties to change, it is apparently not sufficient to do so, instead requiring condition‐specific cues to fulfill its function. In the case of dauer formation, the FoxO transcription factor daf‐16 is a potential, condition‐specific cofactor that may permit UNC‐86 to control remodeling of neurons during entry in the dauer stage (Bhattacharya et al, ) (Figure 4c). During sexual maturation, UNC‐86 may cooperate with male‐specific transcription factors, such as LIN‐29 in AIM or DMD‐3 in PHC, to bring about male‐specific remodeling events (Pereira et al, ; Serrano‐Saiz et al, ) (Figure 4c).…”

Anatomy and activity patterns in a multifunctional motor neuron and its surrounding circuits

“…This is an immensely powerful approach because a single (costly and time consuming) EM run can be used with an unlimited number of functional studies. However, cross-identification of neurons between EM and functional imaging in this approach is ultimately limited by the fact that all nervous systems, even the simplest ones, exhibit considerable variability in their connectomes (Bhattacharya et al, 2019). Accordingly, robustly linking function to connectivity requires a combined anatomical and functional assessment within the same animal (Bargmann and Marder, 2013).…”