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.
KeywordsLong-term depression NMDA receptor Cannabinoid Leech Synaptic plasticity
Analysis of variance
Central nervous system
Excitatory post-synaptic potential
Low frequency stimulation
Metabotropic glutamate receptor
N-methyl-d-aspartic acid receptor
The authors thank Drs. Brenda Moss, Kenneth Muller, Kevin Crisp and Maurice Elphick for their helpful comments and suggestions. Supported by grants from the National Science Foundation (IBN-0432683, BDB), the South Dakota Spinal Cord/Traumatic Brain Injury Research Council (BDB) and by a subproject of the National Institutes of Health grant (P20 RR015567, BDB), which is designated as a Center of Biomedical Research Excellence (COBRE).
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