ASHL, ASHR

Type: Sensory neuron (polymodal nociceptive for osmo-, mechano-, electro-, photo- and odorsensation)
In MoW: ASH
Male Wiring Project: ASHL, ASHR
In Wormbase: ASH, ASHL, ASHR
Lineage: AB plpaappaa, AB prpaappaa
Location: Lateral ganglia of head
Description: Amphid neurons, single (AsH) ciliated endings. Like all other amphid neurons, ASH are born near the presumptive nose of the embryo during development. They then anchor a short projection there, after which the cell body migrates away, stretching the dendrite out behind it. This process is dependent on DEX-1 or DYF-7, secreted extracellular matrix proteins which act cooperatively for anchoring. In mutants lacking these proteins, the dendrite fails to anchor at the nose and is dragged along with the migrating cell body, giving rise to a short dendritic stub (Heiman and Shaham, 2010). Dendritic process takes up FITC. ASH axon projects into the ventral cord by way of the same side amphid commissure and then grows into the nerve ring where it makes diverse synaptic connections in ring neuropil
Neurotransmitter/ Neuropeptide:
- Glutamate
- FLP-21; FMRFamide-like neuropeptide
- INS-1; insulin-like peptide, orthologous to human insulin
- NLP-3; neuropeptide-like peptide
- NLP-15; neuropeptide-like peptide
(Li and Kim, 2008; Rogers et al., 2003; Nathoo et al., 2001; Lee et al., 1999)
Innexin expression:
- INX-4 (in early larva)
- INX-19
(Altun et al., 2009; Chuang et al., 2007)




Receptor expression:
- DCAR-1; seven transmembrane receptor for dihydrocaffeic acid (a water-soluble repellent)
- DOP-4; (D1-like) dopamine receptor
- NPR-1; receptor for flp-18- and flp-21-encoded peptides
- OCTR-1; octopamine receptor
- OCR-2; TRPV (transient receptor potential channel, vanilloid subfamily; mammalian capsaicin receptor-like channel)
- OSM-9; TRPV (transient receptor potential channel, vanilloid subfamily; mammalian capsaicin receptor-like channel)-cation selective. Among "thermoTRPs" (TRPA, TRPM, TRPV)
- SER-3; octopamine receptor
- SER-5; serotonin receptor (5-HT6R-like)
- SRA-6; G protein-coupled seven transmembrane receptor
- SRB-6; G protein-coupled seven transmembrane receptor
- TMC-1; Na+-sensitive ion channel required for salt taste chemosensation and high salt avoidance behavior
- TRPA-1; transient receptor potential ion channel
- TYRA-2; tyramine receptor
- UNC-8; mechanically gated ion channel subunit; amiloride-sensitive Na+ channel (ASC) protein (DEG/ENaC subunit)
(Wormbase; Chatzigeorgiou et al., 2013; Altun, 2011; Ezcurra et al, 2011; Aoki et al., 2011; Tobin et al., 2002; Coates and de Bono , 2002; de Bono M. et al., 2002; Tavernarakis et al., 1997; Troemel et al., 1995)
Function:
- ASH is the main nociceptor and leads to avoidance responses from noxious stimuli, which include hyperosmolarity, nose touch, volatile repellent chemicals (1-octanol), heavy metals (Cd++ and Cu++), detergents/SDS, protons, high salt and alkaloids, such as quinine. There is stimulus-specific downstream signaling in ASH; a mutation in the glutamate receptor subunit, glr-1 which acts in synaptic targets of the ASH neurons, eliminates the response to nose touch but not to osmotic repellents. Similarly, ITR-1 (inositol 1,4,5-trisphosphate receptor) functions in nose touch- and benzaldehyde-avoidance but not in other known ASH-mediated avoidance behaviors. ASH-mediated aversive responses are modulated by monoamines and peptides. Receptors for 5-HT (SER-5), DA (DOP-3, DOP-4), and OA (OCTR-1, SER-3) appear to function directly in the ASH neurons for these effects. Food or 5-HT enhances a subset of ASH-mediated aversive responses (to nose touch, but not to soluble repellants, e.g.) Similarly, DA enhances aversive responses via DOP-4 on ASH, while TA and OA delay or inhibit these reponses through distinct subsets of TA and OA receptors. Inhibition by TA and OA requires the release of multiple neuropeptides from a number of additional neurons. These neuropeptides activate peptide receptors within the ASH-mediated circuit itself and on sensory neurons outside the circuit, suggesting these monoamine-initiated peptidergic signaling cascades can have global effects.
(Chatzigeorgiou et al., 2013; Ezcurra et al., 2011; Komuniecki et al., 2011; Walker et al, 2009; Bargmann, 2006; de Bono & Villu Maricq, 2005; Hilliard et al, 2004; Hiliard et al., 2002; Hart et al., 1999; Sambongi et al., 2000; Sambongi et al., 1999; Troemel et al., 1995; Bargmann et al, 1990; Culotti & Russell 1978).
- Lightsensation (350-470 nm range); when a flash of light is focused on the head of a worm moving forward, the animal halts and initiates reversals. Ablation of ASJ, AWB, ASK and ASH neurons together leads to a severe deficit in this head avoidance response while ablation of them individually or in different combinations does not yiled a significant defect suggesting functional redundancy (Ward et al., 2008).
- Electrosensory navigation; C. elegans moves toward the negative pole of an electric field. Killing the ASJ or ASH neurons leads to significant disruption in electrotaxis while killing ASK, AWB or AWC has a weaker effect (Gabel et al., 2007).
- ASH and ADL are proposed to mediate social feeding behavior in response to repulsive cues (e.g. high O2 levels); ablation of ASH and ADL abolishes social feeding behavior transforming social animals to solitary feeders; avoidance of high O2 levels that facilitate aggregation is promoted by OCR-2 and OSM-9, and the transmembrane protein ODR-4, acting in the nociceptive neurons ASH and ADL. ASH and ADL, in turn, transmit information about aversive stimuli in the environment to a circuit that is responsible for aggregation, rapid locomotion, and food bordering behavior (Rogers et al., 2006; de Bono et al., 2002).
- Modulates innate immune response to pathogenic bacteria. ASH, ASI, AQR, PQR, and URX neurons control the unfolded protein response (UPR) and a p38 mitogen-activated protein kinase signaling pathway required for innate immunity (Singh & Aballay, 2012.) Loss of OCTR-1 signaling in ASH and ASI increases the general immune function of the nematodes; OCTR-1 functions in these neurons to actively suppress innate immune responses by down-regulating the expression of noncanonical UPR genes in nonneuronal tissues (Sun et al., 2011s)
- Plays role in establishment of asymmetric fates of AWCL/R neurons during development via NSY-5/INX-19 gap junctions (Schumacher et al., 2012.)


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ASHL (AB plpaappaa) development in the embryo.
Dorsal view. Bottom is left side of the embryo. Spheres indicate individual nuclei. Black sphere: ancestors of ASHL; dark grey spheres: apoptotic cells; other cells follow the WA color code (after they acquire specific cell or tissue identities). 0 min is fertilization. Click on the movie for higher resolution rendition (by A. Santella & Z. Bao).

 
 

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ASHR (AB prpaappaa) development in the embryo.
Dorsal view. Bottom is left side of the embryo. Spheres indicate individual nuclei. Black sphere: ancestors of ASHR; dark grey spheres: apoptotic cells; other cells follow the WA color code (after they acquire specific cell or tissue identities). 0 min is fertilization. Click on the movie for higher resolution rendition (by A. Santella & Z. Bao).


 
 

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3D reconstruction of the anterior sensory endings (cilia and dendrites) from high resolution serial section transmission electron micrographs (ssTEMs).
Bar 1 μm. Color code for the sensory endings is shown on the right-colors do not follow the WA color code. To expand, double click on the video, to return to original size, click "esc" (Doroquez et al., 2014)

 
 
 

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3D reconstruction of all amphid neuron cilia and associated socket and sheath cell processes.
Modeled from serial section transmission electron micrographs
(ssTEMs). Bar 1 μm. Color code for the sensory endings is shown on the left-colors do not follow the WA color code. To expand, double click on the video, to return to original size, click "esc" (Doroquez et al., 2014)

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