Sunday, August 26, 2012

Neuromodulatory State and Sex Specify Alternative Behaviors through Antagonistic Synaptic Pathways in C. elegans

Jang, H. Kim, K. Neal, SJ. Macosko, E. Kim, D. Butcher, RA. Zeiger, DM. Bargmann, CI. Sengupta, P. (2012) Neuromodulatory State and Sex Specify Alternative Behaviors through Antagonistic Synaptic Pathways in C. elegans. Neuron 75: 585-592.


C9: repulsed - WT hermaphrodites
      attracted - WT males
      neutral - social hermaphrodites (npr-1 mutants)

WT herm: ADL detects C9 drives repulsion through its chemical synapses.
Males: ADL responses diminished. ASK circuit antagonizes repulsion.
Social: ADL response antagonized by RMG hub-spoke circuit.

ocr-2 trpv channels? I guess these are the detectors of some chemicals, used to detect C9 and glycerol. Or this is how they signal downstream...

Figure 1 - knock out ocr-2, prevents C9 avoidance behavior. Rescued when ocr-2 is expressed in ADL. ADL shows calcium response to C9, goes away when ocr-2 is knocked out. Blocking chemical synpatic transmission from ADL prevents C9 avoidance.

Figure 2 - npr-1 mutants are less sensitive to C9 - neutral to low concentrations, but still avoid high-concentrations. RMG circuit competes with ADL chem synapses to push repulsion - additive competition. npr-1 reduces Calcium response of ADL - indirect effects of RMG on ADL. ADL neurons not effected when RMG gap junctions are blocked. Altering chem strength biases avoidance.
Paradox: ADL repulses C9, but involved in aggregation. Solution: ADL repulses through chem synapses, RMG attracts through electrical - aggregation pushes balance towards RMG circuit.
npr-1 acts acutely, turned on by heat-shock.

Figure 3 - ADL Ca responses reduced in amplitude and delayed in males. ASK antagonizes repulsion - males with killed ASK avoid, no change for herms that normally avoid. ADL can drive repulsion if synapses are strengthened in males. Repulsion is inhibited by ASK and RMG.

Figure 4 - npr-1 males are attracted to C9. Manipulating the other parts have similar effects. npr-1 mutants show bigger resopnses to C9 in ASK. ADL circuit activates avoidance, RMG/ASK inhibit avoidance. ASK can sense C3, and mixture of C3 and C9 is neutral to npr-1 herms.


model: ADL chem synapses promote repulsion, RMG gap-junction promotes attraction. "push-pull circuit motif." npr-1 inhibits RMG through unknown mechanism - "it could close the RMG gap junctions to disengage the entire hub-and-spike circuit." RMG potentiates ASK signaling and inhibits ADL signaling.

animals can change attraction/repulsion behaviors depending on behavioral state. Suggesting that npr-1 may be modulated. "reminiscent of the flexible circuit states of crustacean stomch cpgs and vertabrate spinal cord motor circuits."

RMG antagonizes ADL while facilitating ASK. "common network motif can perform distinct computations in ways that are not evident solely from anatomical wiring diagrams." (ASK Ca responses are downward, ADL's are updward).