Two forms of long-term depression in a polysynaptic pathway in the leech CNS: One NMDA receptor-dependent and the other cannabinoid-dependent

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Although long-term depression (LTD) is a well-studied form of synaptic plasticity, it is clear that multiple cellular mechanisms are involved in its induction. In the leech, LTD is observed in a polysynaptic connection between touch mechanosensory neurons (T cells) and the S interneuron following low frequency stimulation. LTD elicited by 450 s low frequency stimulation was blocked by N-methyl-d-aspartic acid (NMDA) receptor antagonists. However, LTD elicited by 900 s low frequency stimulation was insensitive to NMDA receptor antagonists and was instead dependent on cannabinoid signaling. This LTD was blocked by both a cannabinoid receptor antagonist and by inhibition of diacylglycerol lipase, which is necessary for the synthesis of the cannabinoid transmitter 2-arachidonyl glycerol (2-AG). Bath application of 2-AG or the cannabinoid receptor agonist CP55 940 also induced LTD at this synapse. These results indicate that two forms of LTD coexist at the leech T-to-S polysynaptic pathway: one that is NMDA receptor-dependent and another that is cannabinoid-dependent and that activation of either form of LTD is dependent on the level of activity in this circuit.

Original languageEnglish (US)
Pages (from-to)831-841
Number of pages11
JournalJournal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology
Issue number9
StatePublished - Aug 6 2009



  • Cannabinoid
  • Leech
  • Long-term depression
  • NMDA receptor
  • Synaptic plasticity

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Animal Science and Zoology
  • Behavioral Neuroscience

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