Somatosensory circuits, which gather sensory information from the skin and body surface, are a feature of most animal nervous systems. A patch of skin typically contains multiple classes of primary somatosensory neurons with dendrites responding to distinct sensory modalities. Somatosensory circuits include thermosensory neurons responding to temperature, touch neurons responding to gentle pressure or motion, proprioceptors responding to body posture, and nociceptors responding to harsh, body-damaging stimuli. Touch neurons, proprioceptors, and nociceptors share the property that their activities are controlled by mechanical force.
Most, if not all, primary mechanosensory neurons sense force using ion channels that are directly mechanically gated. Many of these channels, particularly in invertebrates, appear to come primarily from one of two protein superfamilies: the TRP channels, and the DEG/ENaC channels (Garcia-Anoveros and Corey, 1997; Goodman et al., 2004
). TRP channels are nonspecific cation channels composed of subunits with six transmembrane α helices. At least some TRP channels appear to be sufficient by themselves to produce touch- or stretch-evoked currents (Christensen and Corey, 2007
). In addition, TRP channels can be activated by G protein signaling, which has been implicated in other sensory transduction processes including taste, vision, and olfaction (Kahn-Kirby and Bargmann, 2006
). In contrast, DEG/ENaC channel subunits have two transmembrane α helices and form channels that are permeable to sodium and, in some cases, calcium (Bounoutas and Chalfie, 2007
). Both families have been implicated in mechanosensory transduction in invertebrates as well as vertebrates.
The process of mechanosensation has been extensively studied in genetically tractable organisms such as C
(Arnadóttir and Chalfie, 2010
). Touch is an important sensory modality for C
; indeed, over 10% of the neurons in the adult hermaphrodite are thought to be mechanoreceptors responding to external touch stimuli (White et al., 1986
). The best studied of these are the five neurons (ALML, ALMR, AVM, PLML, and PLMR) that sense gentle body touch. These cells sense low-threshold mechanical stimuli using a mechanotransduction complex whose core components include the DEG/ENaC channel proteins MEC-4 and MEC-10 and the stomatin MEC-2 (Driscoll and Chalfie, 1991; O'Hagan et al., 2005
). Activation of the ALM and AVM anterior touch neurons triggers a change from forward to backward movement; this escape response appears to depend primarily on gap junctions between the mechanoreceptor neurons and the backward-command interneurons that potentiate backward locomotion (Chalfie et al., 1985
). Conversely, activation of PLM posterior body touch receptors activates forward-command interneurons that promote accelerated forward locomotion. An additional pair of neurons in the body, the PVD multidendritic nociceptors, are required to generate escape responses to harsh body touch (Way and Chalfie, 1989
also respond to touch stimulation on the nose. When an animal collides with an object head-on, it reverses direction in a manner similar to the anterior touch escape reflex. As many as 20 neurons with sensory endings in or around the nose have been implicated by morphological or functional criteria as potential nose touch mechanoreceptors. Cell ablation experiments indicated that loss of either of two neuron pairs, the ASH and FLP neurons, causes a partial reduction in nose touch response, and elimination of both classes results in a strong nose touch defect (Kaplan and Horvitz, 1993
). These results led to the conclusion that ASH and FLP are the primary sensory neurons involved in the nose touch escape reflex. The ASH neurons are polymodal nociceptors that respond to chemical and osmotic stimuli in addition to nose touch (Kaplan and Horvitz, 1993
), and their responses to all these stimuli are dependent on the TRPV channel OSM-9 (Colbert et al., 1997
). The FLPs have highly branched multidendritic arbors that surround the animal's head, suggesting that they may also be nociceptors (Hall and Altun, 2008; Albeg et al., 2011
). The FLPs express the DEG/ENaC channel MEC-10 (Huang and Chalfie, 1994; Chatzigeorgiou et al., 2010b
) as well as the OSM-9 TRPV channel (Colbert et al., 1997
), though, to our knowledge, the effects of these molecules on mechanosensation in the FLPs have not been reported.
Additional neurons have been implicated as nose touch mechanosensors, though their importance in nose touch avoidance behavior is less well established (A). The four OLQ neurons have ciliated endings in the outer labial sensilla that suggest a function as mechanoreceptors. Ablations of the OLQs alone have little effect on nose touch escape responses, though they enhance the defects of ASH and FLP ablations (Kaplan and Horvitz, 1993
). However, the OLQs have been implicated in another nose touch-related behavior, the suppression of lateral “foraging” movements of the head by nose or anterior body touch (Driscoll and Kaplan, 1997; Hart et al., 1995; Alkema et al., 2005; Kindt et al., 2007b
). OLQ ablations also affect the rate and amplitude of foraging in unstimulated animals, suggesting a role in mechanosensory feedback for this behavior. Nose touch evokes calcium transients in the OLQs, which are affected by mutations in the TRPA channel trpa-1
(Kindt et al., 2007b
). The four CEP neurons also have sensory cilia in the nose that indicate a role as mechanoreceptors. Although ablations of the CEPs affect neither nose touch avoidance nor foraging behaviors, they do act with the other dopaminergic neurons to mediate a slowing response to a bacterial lawn, which appears to involve mechanical detection of bacteria (Sawin et al., 2000
). Gentle nose touch evokes neural responses in CEP that require the cell-autonomous activity of the TRPN channel TRP-4 (Kindt et al., 2007a; Kang et al., 2010
). Thus, both the OLQ and CEP neurons appear to sense nose touch; however, their absence primarily affects foraging and slowing behaviors rather than nose touch avoidance.
The FLP Neurons Respond to Harsh Head Touch and Gentle Nose Touch
In this study, we investigate the circuit for C. elegans nose touch avoidance in more detail using a combination of neuroimaging and behavioral analysis. We find that the FLP neurons are polymodal nociceptors that respond to harsh touch as well as heat. In addition, the FLPs respond to gentle touch applied to the more restricted region of the nose. Whereas harsh head touch is dependent only on the cell-autonomous activity of a MEC-10-containing DEG/ENaC complex, gentle nose touch also requires mec-10-independent contributions from other nose touch neurons that are coupled to FLP through gap junctions. Activation of the gentle nose touch neurons thus acts in a circuit-dependent manner to facilitate low-threshold responses in the otherwise high-threshold nociceptor neurons.