Long-term depression of nociceptive synapses by non-nociceptive afferent activity: role of endocannabinoids, Ca²+, and calcineurin

Brain Research
Sharleen Yuan, Brian D Burrell

Abstract

Activity in non-nociceptive afferents is known to produce long-lasting decreases in nociceptive signaling, often referred to as gate control, but the cellular mechanisms mediating this form of neuroplasticity are poorly understood. In the leech, activation of non-nociceptive touch (T) mechanosensory neurons induces a heterosynaptic depression of nociceptive (N) synapses that is endocannabinoid-dependent. This heterosynaptic, endocannabinoid-dependent long-term depression (ecLTD) is observed where the T- and N-cells converge on a common postsynaptic target, in this case the motor neuron that innervates the longitudinal muscles (L-cells) that contributes to a defensive withdrawal reflex. Depression in the nociceptive synapse required both presynaptic and postsynaptic increases in intracellular Ca²⁺. Activation of the Ca²⁺-sensitive protein phosphatase calcineurin was also required, but only in the presynaptic neuron. Heterosynaptic ecLTD was unaffected by antagonists for NMDA or metabotropic glutamate receptors, but was blocked by the 5-HT₂ receptor antagonist ritanserin. Depression was also blocked by the CB1 receptor antagonist rimonabant, but this is thought to represent an effect on a TRPV-like receptor. This heterosynaptic, ...Continue Reading

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Citations

Mar 8, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sharleen Yuan, Brian D Burrell
Jan 31, 2016·Neuropeptides·Noothan Jyothi SatheeshPeter Kruzliak
Jan 13, 2015·Invertebrate Neuroscience : in·Elizabeth Hahn, Brian Burrell
Jun 4, 2013·Molecular Pain·Alexandra HigginsBrian D Burrell
Sep 24, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Riley T Paulsen, Brian D Burrell
Nov 10, 2017·Journal of Neurophysiology·Yanqing Wang, Brian D Burrell
Oct 18, 2014·The Journal of Experimental Biology·Torrie SummersBrian D Burrell
Apr 24, 2021·Journal of Neurochemistry·Andrew J Kesner, David M Lovinger

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