NMDAR-mediated modulation of gap junction circuit regulates olfactory learning in C. elegans

Abstract

Modulation of gap junction-mediated electrical synapses is a common form of neural plasticity. However, the behavioral consequence of the modulation and the underlying molecular cellular mechanisms are not understood. Here, using a C. elegans circuit of interneurons that are connected by gap junctions, we show that modulation of the gap junctions facilitates olfactory learning. Learning experience weakens the gap junctions and induces a repulsive sensory response to the training odorants, which together decouple the responses of the interneurons to the training odorants to generate learned olfactory behavior. The weakening of the gap junctions results from downregulation of the abundance of a gap junction molecule, which is regulated by cell-autonomous function of the worm homologs of a NMDAR subunit and CaMKII. Thus, our findings identify the function of a gap junction modulation in an in vivo model of learning and a conserved regulatory pathway underlying the modulation.

Circumventing neural damage in a C. elegans chemosensory circuit using genetically engineered synapses

“…However, unlike Podr-1 connexin expression (in AWC, AWB, and I1), connexin expression in AWB alone using the Pstr-1 promoter (Troemel et al, 1997) did not restore chemotaxis in worms lacking AIA (Figure 2D), excluding a role for AWB neurons per se in behavioral recovery. In addition, the Pinx-1 promoter that we used for AIB connexin expression has been reported to drive expression in AIY and AIB neurons until the L3 larval stage and then solely in AIB (Altun et al, 2008), and has accordingly been used in several studies for AIB-specific expression (Attreed et al, 2016;Choi et al, 2020;Gordus et al, 2015). We indeed consistently observed specific AIB expression in over 40 worms that we tested (e.g., Figure 2E).…”

Investigating the molecular mechanisms of learning and memory using Caenorhabditis elegans

“…Correspondingly, turning rate was significantly increased in PA14conditioned worms, a phenotype that requires gap junction decoupling of the AIB/AVA/RIM neural circuit (Choi et al, 2020).…”

“…This decoupling was not observed in nmr-1 mutants, whereas AIB/AVA/RIM decoupling occurred normally in inx-4(null);nmr-1 double mutants. Based on these findings, NMR-1 was proposed to facilitate PA14 aversive learning through RIMexpressed UNC-43, which inhibits INX-4-mediated decoupling of gap junctions in the AIB/AVA/RIM neural circuit (Choi et al, 2020).…”

“…This decoupling was not observed in nmr ‐ 1 mutants, whereas AIB/AVA/RIM decoupling occurred normally in inx ‐ 4(null) ; nmr ‐ 1 double mutants. Based on these findings, NMR‐1 was proposed to facilitate PA14 aversive learning through RIM‐expressed UNC‐43, which inhibits INX‐4‐mediated decoupling of gap junctions in the AIB/AVA/RIM neural circuit (Choi et al, 2020). Reverse locomotion is inhibited by AVA cells and promoted by RIM neurons (Alkema et al, 2005; Piggott et al, 2011), whereas AIB activation promotes turning and inhibits forward locomotion (Gray et al, 2005; Wakabayashi et al, 2004), so it is likely that chemo‐/odour‐ taxis is affected by the regulation of these gap junctions.…”

What can a worm learn in a bacteria-rich habitat?

“…This type of learning in the adult C. elegans is contingent on the pathogenicity of the training bacteria and a serotonin signal. The training-dependent change in the olfactory response is specific for the odorants of the training bacteria (Figure 2(A-C)) (Choi, Liu, Wu, Yang, & Zhang, 2020;Ha et al, 2010;Jin et al, 2016;Liu et al, 2018;Zhang et al, 2005). Together, these results indicate a learned association between pathogenicity and the odorants of the training bacterium.…”