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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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Abstract

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.

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Abbreviations

2-AG:

2-Arachidonyl glycerol

AMPA:

α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid

AM251:

1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide

ANOVA:

Analysis of variance

AP5:

2-Amino-5-phosphonopentanoic acid

CNS:

Central nervous system

DMSO:

Dimethyl sulfoxide

EPSP:

Excitatory post-synaptic potential

LFS:

Low frequency stimulation

LTD:

Long-term depression

LTP:

Long-term potentiation

mGluR:

Metabotropic glutamate receptor

MK801:

(5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine

NMDAR:

N-methyl-d-aspartic acid receptor

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Acknowledgments

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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  1. Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, Vermillion, SD, 57069, USA

    Qin Li & Brian D. Burrell

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Correspondence to Brian D. Burrell.

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359_2009_462_MOESM1_ESM.eps

Supplementary Figure 1. The different periods of drug perfusion between preparations that received 450s versus 900s low frequency stimulation did not change the effects of AP5 or AM251 on LTD. AP5 bath-application lasting to 900s (which matches the duration of drug treatment during 900s low frequency stimulation) blocked LTD following 450s low frequency stimulation as effectively as synapses that underwent a 450s drug application that coincided with the 450s low frequency stimulation (one-way ANOVA p<0.001; Newman-Keuls’ test: between 450s and 900s AP5 perfusion vs. no drug, p<0.001*). Neither the 450s nor 900s AM251 perfusion were effective at blocking LTD following 450s low frequency stimulation and neither group differed from synapses that underwent 450s low frequency stimulation in saline with DMSO (one-way ANOVA, ns). DMSO attenuated LTD following 450s low frequency stimulation, but significant depression was still observed. Length of AP5 or AM251 treatment did not alter the effects of either drug on LTD of the electrical synaptic component (Data not shown). (EPS 976 kb)

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Li, Q., Burrell, B.D. Two forms of long-term depression in a polysynaptic pathway in the leech CNS: one NMDA receptor-dependent and the other cannabinoid-dependent. J Comp Physiol A 195, 831–841 (2009). https://doi.org/10.1007/s00359-009-0462-3

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  • DOI: https://doi.org/10.1007/s00359-009-0462-3

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