[
International Worm Meeting,
2021]
Sexually reproducing animals display sexually dimorphic behaviors, geared towards reproductive success. Are there differences in the way the two sexes interpret and respond to the same aversive input? To address this question we analyzed the worm's avoidance responses to hazardous conditions. C. elegans generates an escape response to aversive stimuli by integrating sensory information from the polymodal nociceptive ASH head neurons and tail neurons, and conveying it to the main reversal interneuron AVA. The recent full mapping of the male connectome (Cook et al. 2019) suggests that the sex-shared neurons in the avoidance circuit are dimorphically connected, e.g. ASH to AVA connection is predicted to exist only in hermaphrodites. We measured the response of both sexes to the aversive stimuli SDS and glycerol using a behavioral tail-drop assay. We found that the two sexes exhibit dose-dependent sexually dimorphic responses to the aversive stimuli - across multiple nociceptive modalities, hermaphrodites exhibited a lower pain threshold than males. The behavioral differences and the suggested anatomical maps prompted us to functionally deconstruct the avoidance circuit. To examine potential sexual dimorphism at the sensory level, we compared ASH receptor expression levels (OCR-2, OSM-9, OSM10, QUI-1, ODR-3, GPA-3), ASH glutamatergic secretion by imaging the pHluorin sensor, and neuronal activation by calcium imaging in both sexes. We found that the ASH sensory neuron is non-dimorphic for all these parameters and responds similarly in the two sexes. Furthermore, we activated ASH optogenetically, thus bypassing the sensory input level, and found that hermaphrodites responded with a reversal at a lower LED intensity compared to males, in agreement with the tail-drop assay. Lastly, imaging of the downstream AVA interneuron revealed a stronger and longer response to the stimulus in hermaphrodites compared to males, further pointing to the connectivity and interneuron levels as the key sources for dimorphism in the circuit. Together, our results suggest that dimorphic responses to noxious cues arise due to neuronal circuit dimorphism downstream of sensory processing. We hypothesize that differences in circuit connectivity, rather than sensory perception per se, allow for sex-specific behavioral adaptation.
[
International Worm Meeting,
2021]
The nature of the relationship between neural circuits and the resulting animal behavior is a key question in neurobiology. It was previously established that the specific synaptic and cellular properties of neural networks can be widely disparate, yet maintain similar function (Prinz et al., 2004). It is therefore clear that some features of a network's structure are important to retain certain functional features. The sensitivity of such networks to changes in the topology have not been characterized. To explore the contribution of topology to the network's performance, we focused here on the circuit for nociceptive behaviors in C. elegans. The neurons of the circuit are shared between the two sexes, but their connectivity is different (Cook et al., 2019). The behaviors that result from these circuits are sexually dimorphic as well. The distinct network topologies and behavioral outputs make this circuit a good example for exploring the relationship between structure and function in neural networks. We simulated the response of the nociceptive circuits to external stimuli, in males and in hermaphrodites, using a wide range of realistic values for the circuit's biophysical parameters (synaptic strengths, conductivity, membrane time constants, etc.). We then searched for the parameters' space in which the activity of the motor output neurons in the simulation would match the worms' behaviors in experimental observations. We found an overlap between the sexes in terms of the synaptic and cellular parameters that allow for the correct behavior of the network. Moreover, our results suggest that the connectivity alone might be sufficient to explain the behavioral differences between the sexes. Notably, more stringent requirements of the models' performance suggests that the connections in this network cannot be all excitatory, as has been commonly assumed, or that additional inhibitory neurons must play an important role in shaping the circuit's response to tail stimulation. Future analysis will further explore the relations between the network's topology and the joint activity patterns of the neurons as measured by calcium imaging.