|
Neurotransmitters in Caenorhabditis elegans
See Neurotransmitter criteria. This table
addresses criterion I.
Acetylcholine (ACh)
Serotonin (5HT)
Dopamine (DA)
Tyramine (TA)
Octopamine (OA)
Glutamate (Glu)
Gamma-aminobutyric acid (GABA)
| ACETYLCHOLINE (ACh) |
DESCRIPTION |
GENE NAME |
TECHNIQUE FOR DETECTION |
LOCALIZATION |
REFERENCES |
| ACh |
NA |
Radioenzymatic assay |
Whole animal |
Hosono et al., 1987; Hosono & Kamiya, 1991; Nguyen et al., 1995 |
Synthesis
 |
| Choline Acetyltransferase (ChAT) |
cha-11
|
Enzymatic assay |
Whole animal |
Rand & Russell, 1985 |
| Choline Acetyltransferase (ChAT) |
cha-11
|
Antibody |
IL2, URA, URB, SAA, SAB, SIA, SIB, SMB, SMD, RMD, RIM, M1, M2, M5, I1 (faint), I6 (faint), VAn, VBn, VCn, DAn, DBn, ASn, SDQ, HSN (faint, h), ALN, PLN, others. |
Duerr et al., 2008 |
| Transport |
| Vesicular Acetylcholine Transporter (VAChT) |
unc-171
|
Antibody |
Same as cha-1 |
Duerr et al., 2008 |
| Choline Transporter (HAChT / ChT) |
cho-1
|
Reporter transgenics |
Cholinergic neurons |
Matthies et al., 2006 |
| Postsynaptic Choline/Acetylcholine Transporter |
snf-6
|
Reporter transgenics |
Body wall muscle, vulval and enteric muscles, a few unidentified neurons |
Kim et al., 2004 |
| Catabolism |
| Acetylcholinesterase (AChE) |
NA |
Histochemistry2 |
Strong, reliable staining in nerve ring, ventral ganglion, pharyngeal-intestinal valve and anal depressor region;
more variable staining in VNC, DNC and PAG |
Culotti et al., 1981 |
| Acetylcholinesterase (AChE) class A |
ace-1
|
Enzymatic assay |
Whole animal |
Johnson et al., 1981; Culotti et al., 1981 |
| Acetylcholinesterase (AChE) class B |
ace-2
|
Enzymatic assay |
Whole animal |
Johnson et al., 1981; Culotti et al., 1981 |
| Acetylcholinesterase (AChE) class C |
ace-3
|
Enzymatic assay |
Whole animal |
Johnson et al., 1981; Culotti et al., 1981 |
| Acetylcholinesterase (AChE) |
ace-1
|
Reporter transgenics |
- |
Combes et al., 2000; Combes et al., 2003 |
| Acetylcholinesterase (AChE) |
ace-2
|
Reporter transgenics |
- |
Combes et al., 2000; Combes et al., 2003 |
| Acetylcholinesterase (AChE) |
ace-3
|
Reporter transgenics |
- |
Combes et al., 2000; Combes et al., 2003 |
| Acetylcholinesterase (AChE) |
ace-4
|
Reporter transgenics |
- |
Combes et al., 2000; Combes et al., 2003 |
Related mutant phenotypes
| ACh |
cha-1
|
ACh levels reduced or absent |
Hosono et al., 1987 |
| ACh |
unc-17
|
ACh levels elevated |
Hosono et al., 1987 |
| ChAT |
cha-1
|
ChAT enzymatic activity is reduced or absent |
Rand & Russell 1984; Hosono et al., 1987 |
| Acetylcholinesterase (AChE) |
ace-1, ace-2 |
Histochemical staining2 is reduced in ace-2 mutants, and completely eliminated in ace-2; ace-1 double mutants. |
Culotti et al., 1981 |
| Notes
|
|
| SEROTONIN (5-hydroxytryptamine, 5HT) |
DESCRIPTION |
GENE NAME |
TECHNIQUE FOR DETECTION |
LOCALIZATION |
REFERENCES |
| 5HT |
NA |
HPLC + ED |
Whole animal |
Sanyal et al., 2004 |
| 5HT |
NA |
Formaldehyde induced fluorescence (FIF) |
NSM |
Horvitz et al., 1982 |
| 5HT |
NA |
Antibody |
NSM, ADF, AIM, RIH, HSN (h), CP1-6 (m), RPAG1 (m), RNs 1B, 3B, 9B (m) |
Desai et al., 1988; Loer & Kenyon, 1993; Rand & Nonet, 1997; Jia & Emmons, 2006 |
Synthesis
 |
| Tryptophan Hydroxylase (TPH) |
tph-1
|
Reporter transgenics |
NSM, ADF, [AIM, RIH,]2 HSN (h), CP1-6 (m), RPAG1 (m), RNs 1B, 3B, 9B (m) |
Sze et al., 2000 |
| GTP Cyclohydrolase I (GTP-CH1)3 |
cat-4
|
Reporter transgenics |
NSM, ADF, HSN (h), CP1-6 (m), RNs 1B, 3B, 9B (m) [also expressed in dopaminergic neurons] |
Sze et al., 2002 ; Flames & Hobert, 2009 |
| Aromatic L-Amino Acid Decarboxylase (AADC)4 |
bas-1
|
Reporter transgenics |
NSM, ADF, [AIM, RIH,]2 HSN (h), CP1-6 (m), RPAG1 (m), RNs 1B, 3B, 9B (m)
[also expressed in dopaminergic neurons] |
Hare & Loer, 2004; Flames & Hobert, 2009 |
| Transport |
| Vesicular Monoamine Transporter (VMAT) |
cat-1
|
Reporter transgenics |
NSM, ADF, AIM, RIH, HSN (h), CP1-6 (m), RPAG1 (m), RNs 1B, 3B, 9B (m)
[also expressed in dopaminergic neurons] |
Duerr et al., 1999; Nurrish et al., 1999; Flames & Hobert, 2009 |
| Serotonin Reuptake Transporter (SERT) |
mod-5
|
- |
- |
Ranganathan et al., 2001 |
| Catabolism |
| Monoamine Oxidase (MAO) |
amx-1
|
Reporter transgenics |
Nervous system |
Filkin et al., 2007 |
| MAO |
amx-2
|
Reporter transgenics |
Intestine, neurons |
Filkin et al., 2007 |
| MAO |
amx-3
|
- |
- |
Filkin et al., 2007 |
| Serotonin N-Acetyltransferase (SNAT) |
- |
Enzymatic assay |
Whole animal |
Muimo & Isaacs, 1993 |
Related mutant phenotypes
| TPH |
tph-1 |
Mutant lacks serotonin immunoreactivity |
Sze et al., 2000 |
| GTP-CH1 |
cat-4 |
Mutant lacks serotonin immunoreactivity [and dopamine by FIF] |
Desai et al., 1988; Sulston et al., 1975 |
| AADC |
bas-1 |
Mutant lacks serotonin immunoreactivity (or is greatly reduced); serotonin immunoreactivity is rescued by exogenous 5HT but not 5HTP (5-hydroxytryptophan); see also dopamine-related phenotypes below |
Loer & Kenyon, 1993; Weinshenker et al., 1995; Sawin et al., 2000 |
| VMAT |
cat-1 |
Mutant lacks serotonin FIF in NSM processes, but shows increased FIF in somas; reduced serotonin immunoreactivity; see also dopamine-related phenotypes below |
Horvitz et al., 1982; Loer & Kenyon, 1993 |
| SERT |
mod-5 |
Mutant phenotype consistent with increased presynaptic serotonin, phenocopied by serotonin-specific reuptake inhibitors (SSRIs) such as fluoxetine, partially phenocopied by less-specific tricyclics such as imipramine (norepinephrine reuptake inhibitor, serotonin reuptake inhibitor, eag (K+ channel)-blocker) |
Horvitz et al., 1982; Ranganathan et al., 2001 |
Notes
1 The male-specific, unpaired preanal ganglion neuron on the right side (RPAG) is not identified, but is likely PDC or PGA.
2 Expression of tph-1 and bas-1 in these cells is rare.
3 GTP-CH1 catalyzes the first step in synthesis of tetrahydrobiopterin (BH4), an essential cofactor of aromatic amino acid hydroxylases (including TPH and TH); it is therefore required for synthesis of serotonin and dopamine.
4 AADC is also known as 5HTP Decarboxylase or Dopa Decarboxylase (DDC).
|
|
| DOPAMINE (3-hydroxytyramine, DA) |
DESCRIPTION |
GENE NAME |
TECHNIQUE FOR DETECTION |
LOCALIZATION |
REFERENCES |
| DA |
NA |
HPLC + ED |
Whole animal |
Sanyal et al., 2004 |
| DA |
NA |
Formaldehyde induced fluorescence (FIF) |
CEPD, CEPV, ADE, PDE, RNs 5A, 7A, 9 (m) |
Sulston et al., 1975 |
Synthesis
 |
| Tyrosine Hydroxylase (TH) |
cat-2
|
Reporter transgenics |
CEPD, CEPV, ADE, PDE, RNs 5A, 7A, 9A (m) |
Lints & Emmons, 1999; Flames & Hobert, 2009 |
| GTP Cyclohydrolase I (GTP-CH1) |
cat-4
|
Reporter transgenics |
CEPD, CEPV, ADE, PDE, RNs 5A, 7A, 9A (m) [also expressed in serotonergic neurons] |
Sze et al., 2002 ; Flames & Hobert, 2009 |
| Aromatic L-Amino Acid Decarboxylase (AADC) |
bas-1
|
Reporter transgenics |
CEPD, CEPV, ADE, PDE, RNs 5A, 7A, 9A (m) [also expressed in serotonergic neurons] |
Hare & Loer, 2004; Flames & Hobert, 2009 |
| Transport |
| Vesicular Monoamine Transporter (VMAT) |
cat-1
|
Reporter transgenics |
CEPD, CEPV, ADE, PDE, RNs 5A, 7A, 9A (m) [also expressed in serotonergic neurons] |
Duerr et al., 1999; Nurrish et al., 1999; Flames & Hobert, 2009 |
| Dopamine Reuptake Transporter (DAT) |
dat-1
|
Reporter transgenics |
CEPD, CEPV, ADE, PDE, RNs 5A, 7A, 9A (m) |
Jayanthi et al, 1998; Nass et al, 2001; Flames & Hobert, 2009 |
| Dopamine Reuptake Transporter (DAT) |
dat-1
|
Antibody |
CEPD, CEPV, ADE, PDE, RNs 5A, 7A, 9A (m) |
McDonald et al, 2007 |
| Catabolism - likely uses MAO like serotonin above |
Related mutant phenotypes
|
| DA |
cat-1, cat-2, cat-4 |
DA levels (by HPLC + ED) are reduced to about 40% of wildtype in each of these three mutants |
Sanyal et al., 2004 |
| GTP-CH1 |
cat-4 |
Mutant lacks dopamine by FIF [and serotonin immunoreactivity] |
Sulston et al., 1975; Desai et al., 1988 |
| TH |
cat-2 |
Mutant lacks dopamine by FIF |
Sulston et al., 1975 |
| AADC |
bas-1 |
Mutant lacks dopamine by FIF; DA cells do not become serotonin-immunoreactive with 5HTP treatment; see other serotonin-related phenotypes above |
Sawin et al., 2000; Loer & Kenyon, 1993 |
| VMAT |
cat-1 |
Dopamine by FIF is reduced in processes and increased in somas; mutant is phenocopied by reserpine (VMAT blocker); see serotonin-related phenotypes above |
Sulston et al., 1975 |
| TYRAMINE (TA) |
DESCRIPTION |
GENE NAME |
TECHNIQUE FOR DETECTION |
LOCALIZATION |
REFERENCES |
| TA |
NA |
TLC |
Whole animal |
Alkema et al., 2005 |
Synthesis
 |
| Tyrosine Decarboxylase (TDC) |
tdc-1
|
Reporter transgenics, Antibody |
RIM, UV1 |
Alkema et al., 2005 |
| Transport - likely also uses VMAT like serotonin and dopamine above |
| Catabolism - likely also uses MAO like serotonin and dopamine above |
Related mutant phenotypes
|
| TA |
tdc-1 |
TA (by TLC) is absent in this mutant |
Alkema et al., 2005 |
| OCTOPAMINE (OA) |
DESCRIPTION |
GENE NAME |
TECHNIQUE FOR DETECTION |
LOCALIZATION |
REFERENCES |
| OA |
NA |
Radioenzymatic assay1 |
Whole animal |
Horvitz et al., 1982 |
| OA |
NA |
HPLC + ED |
Whole animal |
Alkema et al., 2005 |
Synthesis
 |
| Tyrosine Decarboxylase (TDC) |
tdc-1
|
Reporter transgenics, Antibody |
RIC, gonadal sheath cells |
Alkema et al., 2005 |
| Tyrosine Decarboxylase (TDC) |
tdc-1
|
Enzymatic assay |
Whole aminal |
Alkema et al., 2005 |
| Tyramine Beta-Hydroxylase (TBH) |
tbh-1
|
Reporter transgenics, Antibody |
RIC, gonadal sheath cells |
Alkema et al., 2005 |
| Transport - likely also uses VMAT like serotonin and dopamine above |
| Catabolism - likely also uses MAO like serotonin and dopamine above |
Related mutant phenotypes
|
| OA |
tdc-1, tbh-1 |
OA (by HPLC+ ED) is absent in these mutants |
Alkema et al., 2005 |
| TDC |
tdc-1 |
TDC enzymatic activity is absent or strongly reduced |
Alkema et al., 2005 |
| TDC |
tdc-1 |
TDC immunoreactivity absent in mutant |
Alkema et al., 2005 |
| TBH |
tbh-1 |
TBH immunoreactivity absent in mutant |
Alkema et al., 2005 |
Notes
|
| GLUTAMATE (Glu) |
DESCRIPTION |
GENE NAME |
TECHNIQUE FOR DETECTION |
LOCALIZATION |
REFERENCES |
| Transport |
| Vesicular Glutamate Transporter (VGluT)1 |
eat-4
|
Reporter transgenics |
M3, NSM, I5(?), ADA, ALM, ASH, ASK, AUA, AVJ or AIN, AVM, FLP, IL1, LUA, OLL, OLQ, PLM, PVD, PVR |
Lee et al., 1999 |
| Plasma Membrane Glutamate Transporter (PmGluT) |
glt-12
|
Reporter transgenics |
Muscle, hypodermis |
Mano et al., 2007 |
| PmGluT |
glt-3
|
Reporter transgenics |
Excretory canal cell, pharynx |
Mano et al., 2007 |
| PmGluT |
glt-4
|
Reporter transgenics |
AUA, RIA, IL2 |
Mano et al., 2007 |
| PmGluT |
glt-5
|
Reporter transgenics |
Pharynx |
Mano et al., 2007 |
| PmGluT |
glt-6
|
Reporter transgenics |
Excretory canal cell, pharynx |
Mano et al., 2007 |
| PmGluT |
glt-7
|
Reporter transgenics |
Excretory canal cell |
Mano et al., 2007 |
Notes
1 EAT-4 is similar to mammalian brain-specific, sodium-dependent inorganic phosphate transporter (BNPI),
now believed to act as a vesicular glutamate transporter.
2 There is no glt-2 (the sequence originally named glt-2 was found to be a splice variant of glt-1), although all glt genes are listed here, it seems unlikely that all are involved in neuronal glutamate use.
|
| GAMMA-AMINOBUTYRIC ACID (GABA) |
DESCRIPTION |
GENE NAME |
TECHNIQUE FOR DETECTION |
LOCALIZATION |
REFERENCES |
| GABA |
NA |
Antibody |
DDn, VDn, RME, AVL, RIS, DVB |
McIntire et al., 1993b |
Synthesis
 |
| Glutamate Decarboxylase (GAD) |
unc-25
|
Reporter transgenics |
DDn, VDn, RME, AVL, RIS, DVB |
Jin et al., 1999 |
| Transport |
| Vesicular GABA Transporter (VGAT) |
unc-47
|
Reporter transgenics |
DDn, VDn, RME, AVL, RIS, DVB |
McIntire et al., 1997 |
| GABA Transporter (GAT) |
snf-11
|
Reporter transgenics, antibody |
RME, AVL, RIS, DVB , RID, 2 neurons in pharynx, 2 neurons in RVG, muscles |
Jiang et al., 2005 ; Mullen et al., 2006 |
| Catabolism |
| GABA Transaminase (GABA-T)1 |
gta-1
|
Reporter transgenics |
Body wall muscle, head neurons, unidentified cells |
none |
| Succinic Semialdehyde Dehydrogenase (SSADH)1 |
alh-7
|
Reporter transgenics, antibody |
Intestine, rectal gland cells, hypodermis, nervous system, head neurons |
none |
Related mutant phenotypes
| GAD |
unc-25 |
lacks GABA immunoreactivity |
McIntire et al., 1993b |
Notes
1 Although both GABA-T and SSADH are important in GABA catabolism in the mammalian brain, there is currently no evidence they are important in C. elegans GABA metabolism (i.e., no revealing mutant phenotypes).
|
|
Abbreviations:
Anatomical: (DNC) dorsal nerve cord; (h) hermaphrodite; (m) male; (PAG) preanal ganglion; (RVG) retrovesicular ganglion; (VNC) ventral nerve cord.
Methodological: (HPLC) high performance liquid chromatography; (ED) electrochemical detection; (TLC) thin layer chromatography; (FIF) formaldehyde induced fluorescence
Beside primary sources listed in the table above, other sites and reviews of C. elegans literature were helpful in assembling this information, including the following:
For information on the criteria for assigning a chemical neurotransmitter function in C. elegans see Neurotransmitter criteria.
To see all monoamine synthesis and degradation pathways refer to Monoamine Pathways Chart.
This section should be cited as: Loer, C.§ 2010. Neurotransmitters in Caenorhabditis elegans, in WormAtlas. doi:10.3908/wormatlas.5.200
§To whom correspondence should be addressed. Curtis Loer: cloer@sandiego.edu |
|
