Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception and avoidance in Caenorhabditis elegans

Abstract

Sensory modulation is essential for animal sensations, behaviours and survival. Peripheral modulations of nociceptive sensations and aversive behaviours are poorly understood. Here we identify a biased cross-inhibitory neural circuit between ASH and ASI sensory neurons. This inhibition is essential to drive normal adaptive avoidance of a CuSO 4 (Cu 2 þ ) challenge in Caenorhabditis elegans. In the circuit, ASHs respond to Cu 2 þ robustly and suppress ASIs via electro-synaptically exciting octopaminergic RIC interneurons, which release octopamine (OA), and neuroendocrinally inhibit ASI by acting on the SER-3 receptor. In addition, ASIs sense Cu 2 þ and permit a rapid onset of Cu 2 þ -evoked responses in Cu 2 þ -sensitive ADF neurons via neuropeptides possibly, to inhibit ASHs. ADFs function as interneurons to mediate ASI inhibition of ASHs by releasing serotonin (5-HT) that binds with the SER-5 receptor on ASHs. This elaborate modulation among sensory neurons via reciprocal inhibition fine-tunes the nociception and avoidance behaviour.

Co-option of neurotransmitter signaling for inter-organismal communication in C. elegans

“…Our data suggests that ASE and ASI sensory neurons may regulate ASH sensitivity during osas#9 avoidance serving as modulators at the sensory level, similar to previously observed cross inhibition of ASI and ASH neuronal activity in avoidance to copper, and decision making based on physiological state (73,74). Alternatively, these neurons could be interacting with ASH neuronal targets in the osas#9 response, strengthening or dampening the relayed signal, possibly through peptidergic or aminergic signaling to establish the functional circuit.…”

Distinct Roles of Sensory Neurons in Mediating Pathogen Avoidance and Neuropeptide-Dependent Immune Regulation

“…ASI neurons are known to control dauer formation and chemotaxis, whereas ASH neurons regulate nociception, such as osmotic avoidance, chemical avoidance, and social feeding. Recent studies indicate the presence of a reciprocal inhibitory neural circuit comprising the ASI and ASH neurons in C. elegans to modulate Cu 2+ nociception and avoidance behavior (Guo et al, 2015). In addition, there are synaptic connections between ASH and ASI neurons, suggesting that these two neurons might work collaboratively to coordinate behavior, development, energy consumption, and immunity in response to danger signals from the environment such as pathogenic bacteria (Figure 4G).…”

TMC-1 Mediates Alkaline Sensation in C. elegans through Nociceptive Neurons

“…Bath solution (pH 12) was perfused towards the nose tip using a microfluidic system. As ASH neurons are alkali-sensitive and are also functionally connected to ASI neurons (Guo et al, 2015), imaging experiments were performed on worms with ASH ablated using a laser microbeam. tmc-1 cDNA was expressed in ASI under the sra-6 promoter.…”

“…tmc-1 cDNA was expressed in ASI as a transgene with the sra-6 promoter. As ASH neurons express robust alkali-activated currents and are functionally connected to ASI (Guo et al, 2015), we mechanically removed ASH neurons prior to recording ASI. Little if any alkali-activated currents were detected in ASI neurons of worms carrying no tmc-1 transgene (A).…”