Mass‐Spectrometric Identification of Anandamide and 2‐Arachidonoylglycerol in Nematodes

Lehtonen, Marko; Reisner, Kaja; Auriola, Seppo; Wong, Garry; Callaway, J. C.

doi:10.1002/cbdv.200890208

Cited by 41 publications

(40 citation statements)

References 35 publications

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“…These results agree with previous studies in which eCB-LTD in a leech nociceptive synapse was prevented by inhibition of postsynaptic 2-AG synthesis (Yuan and Burrell 2010a). Endocannabinoid transmitters are evolutionarily well conserved, with 2-AG being the most abundant endocannabinoid in the CNS of both vertebrates and invertebrates (Matias et al 2001;Elphick and Egertova 2005;Lehtonen et al 2008;Leung et al 2008). Furthermore, endocannabinoiddependent synaptic modulation has been observed in invertebrate nervous systems (Lemak et al 2007;Burrell 2009, 2010;Yuan and Burrell 2010a).…”

Section: Properties Of Ecb-ltdsupporting

confidence: 92%

Associative, bidirectional changes in neural signaling utilizing NMDA receptor- and endocannabinoid-dependent mechanisms

Li¹,

Burrell²

2011

Learn. Mem.

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Persistent, bidirectional changes in synaptic signaling (that is, potentiation and depression of the synapse) can be induced by the precise timing of individual pre-and postsynaptic action potentials. However, far less attention has been paid to the ability of paired trains of action potentials to elicit persistent potentiation or depression. We examined plasticity following the pairing of spike trains in the touch mechanosensory neuron (T cell) and S interneuron (S cell) in the medicinal leech. Long-term potentiation (LTP) of T to S signaling was elicited when the T-cell spike train preceded the S-cell train. An interval 0 to +1 sec between the T-and S-cell spike trains was required to elicit long-term potentiation (LTP), and this potentiation was NMDA receptor (NMDAR)-dependent. Long-term depression (LTD) was elicited when S-cell activity preceded T-cell activity and the interval between the two spike trains was 20.2 sec to 210 sec. This surprisingly broad temporal window involved two distinct cellular mechanisms; an NMDAR-mediated LTD (NMDAR-LTD) when the pairing interval was relatively brief (,21 sec) and an endocannabinoid-mediated LTD (eCB-LTD) when longer pairing intervals were used (21 to 210 sec). This eCB-LTD also required activation of a presynaptic transient receptor potential vanilloid (TRPV)-like receptor, presynaptic Ca 2+ release from intracellular stores and activation of voltage-gated Ca 2+ channels (VGCCs). These findings demonstrate that the pairing of spike trains elicits timing-dependent forms of LTP and LTD that are supported by a complex set of cellular mechanisms involving NMDARs and endocannabinoid activation of TRPV-like receptors.[Supplemental material is available for this article.]Associative forms of long-term neuroplasticity, as first proposed by Hebb (1949), depend on the temporal relationship between pre-and postsynaptic activity. Studies of spike-timing-dependent plasticity (STDP) have provided experimental confirmation of this principle, specifically that in most connections long-term potentiation (LTP) is produced when a presynaptic action potential (or spike) precedes the postsynaptic spike, whereas long-term depression (LTD) is produced when the order is reversed (see review by Caporale and Dan 2008). In addition to the temporal order being important in determining the sign of the synaptic change, temporal proximity is also critical in that the time between the pre-and postsynaptic activity must be sufficiently brief, usually ,40 msec, to support potentiation or depression.It has been noted that the time intervals between pre-and postsynaptic activity that support STDP are not as long as those observed in many associative learning experiments, in which interstimulus intervals on the scale of seconds can be used to elicit successful conditioning (Drew and Abbott 2006). Most studies of STDP involve pairing single pre-and postsynaptic spikes or brief bursts of two to three spikes; however, many neurons communicate using relatively long trains of action potentials that are tens...

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Section: Properties Of Ecb-ltdsupporting

confidence: 92%

Associative, bidirectional changes in neural signaling utilizing NMDA receptor- and endocannabinoid-dependent mechanisms

Li¹,

Burrell²

2011

Learn. Mem.

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“…However, anandamide and 2-AG were not detected in a mutant strain of C. elegans (fat-3) that lacks functional activity of the delta-6 desaturase enzyme required for synthesis of long-chain polyunsaturated fatty acids (PUFAs; including arachidonic acid) [134].…”

Section: Review Evolution and Comparative Neurobiology M R Elphickmentioning

confidence: 99%

The evolution and comparative neurobiology of endocannabinoid signalling

Elphick

2012

Phil. Trans. R. Soc. B

153

137

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CB 1 -and CB 2 -type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB 1 -type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB 1 /CB 2 -type receptors originated in a common ancestor of extant chordates, and in the sea squirt Ciona intestinalis a CB 1 / CB 2 -type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB 1 /CB 2 -type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB 1 /CB 2 -mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids.

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“…PTZ-induced hyperactivity was prevented by co-treatment with the endocannabinoid 2-AG. As in the mammalian CNS, 2-AG is the most abundant endocannabinoid in the leech CNS and both 2-AG and anandamide are known to be present in other invertebrates (De Petrocellis et al 1999;Matias et al 2001;Lehtonen et al 2008;Elphick 2012). Endocannabinoids have been proposed as a potential therapeutic approach for treating epilepsy, presumably due to their ability to elicit persistent depression of glutamatergic synapses (Marsicano et al 2003;Katona and Freund 2008;Izzo et al 2009;Bhaskaran and Smith 2010;Zurolo et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the medicinal leech

Hahn

Burrell

2015

Invert Neurosci

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This study examined the capacity of a known pro-epileptic drug, pentylenetetrazol (PTZ), to elicit seizure-like activity in the medicinal leech, Hirudo verbana. During in vivo experiments, PTZ elicited increased motor activity in a concentration-dependent manner with the highest concentration (10 mM) eliciting episodes of highly uncoordinated exploratory and swimming behavior. Co-application of the anti-epileptic drug, phenytoin, failed to reduce the absolute amount of PTZ-induced motor behavior, but was able to prevent expression of abnormal exploratory and swimming behaviors. During in vitro experiments in which extracellular recordings of connective nerve activity were made, bath application of 1 μM PTZ in Mg(2+)-free saline elicited a significant increase in spontaneous activity. This PTZ-induced increase in activity was completely inhibited by phenytoin. Interestingly, PTZ-induced hyperactivity was also blocked by co-application of the endocannabinoid 2-arachidonoyl glycerol and the selective serotonin re-uptake inhibitor (SSRI) fluoxetine. These findings suggest that the leech can be a useful system in which to study potential anti-epileptic treatments.

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Mass‐Spectrometric Identification of Anandamide and 2‐Arachidonoylglycerol in Nematodes

Cited by 41 publications

References 35 publications

Associative, bidirectional changes in neural signaling utilizing NMDA receptor- and endocannabinoid-dependent mechanisms

Associative, bidirectional changes in neural signaling utilizing NMDA receptor- and endocannabinoid-dependent mechanisms

The evolution and comparative neurobiology of endocannabinoid signalling

Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the medicinal leech

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