Interaction between NMDA Receptor- and Endocannabinoid-Mediated Modulation of Nociceptive Synapses

Sharleen Yuan,Brian D Burrell

doi:10.1038/s41598-018-37890-z

Sharleen Yuan, Brian D Burrell

Open Access

https://doi.org/10.1038/s41598-018-37890-z

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Journal: Scientific Reports	Publication Date: Feb 4, 2019
Citations: 4	License type: open-access

Affiliation: University of South Dakota

Abstract

Nociceptors, sensory neurons that detect damage or potential damage to the body, are the first stage of communicating noxious stimuli from the periphery to central nervous system (CNS). In this study, long-term potentiation (LTP) in the CNS of the medicinal leech, Hirudo verbana, was examined, taking advantage of the ability to selectively record from nociceptive synapses in this model organism. High frequency stimulation (HFS) of nociceptors produced a persistent increase in synaptic transmission and this LTP was both NMDA receptor-mediated and synapse-specific. Surprisingly, inhibition of NMDA receptors during HFS “uncovered” a persistent form of depression. This long-term depression (LTD) was mediated by the endocannabinoid 2-arachidonoyl glycerol (2-AG) acting on a TRPV (transient receptor potential vanilloid) –like channel. These observations suggest that (1) NMDA receptor mediated LTP is observed in nociceptors across both vertebrate and invertebrate phyla and (2) there may be an interaction between NMDA receptor-mediated and endocannabinoid-mediated forms of synaptic plasticity in nociceptors. Specifically, the NMDA receptor mediated processes may suppress endocannabinoid signaling. Such findings could be significant for understanding cellular mechanisms behind nociceptive sensitization and perhaps their contribution to chronic pain.

Highlights

Patterns of stimulation are required for long-term potentiation (LTP) in different nociceptive pathways[11,15,16] and questions as to whether NMDAR-LTP in spinal nociceptive synapses exhibit synapse specificity similar to what is observed in other regions of the CNS19
Together these results demonstrate that High frequency stimulation (HFS) on a single nociceptor elicits homosynaptic LTP that is synapse specific
NMDAR-LTP has been observed in nociceptive synapses in the mammalian spinal cord, different nociceptive pathways appear to require different patterns of activity to elicit LTP15,47

Summary

Introduction

Patterns of stimulation are required for LTP in different nociceptive pathways[11,15,16] and questions as to whether NMDAR-LTP in spinal nociceptive synapses exhibit synapse specificity similar to what is observed in other regions of the CNS19. Hirudo nociceptive sensory neurons (N cells) have glutamatergic synaptic input to motor neurons and interneurons responsible for reflexive withdrawal and locomotory escape behaviors[6,24,25]. These N cells have input onto serotonergic cells that play a critical role in modulating Hirudo behaviors in the context of learning and responses to stress and hunger[26,27,28,29]. Hirudo pressure (P) cell and touch (T) cell synapses do undergo LTP that is NMDAR-dependent and synapse specific[14,30,31], but LTP in the leech N cell synapses has not been investigated. We found evidence supporting the presence of LTP in these nociceptive synapses that is NMDAR-dependent and synapse-specific, and found, to our surprise, evidence of an interaction between NMDAR-mediated synaptic potentiation and endocannabinoid-mediated synaptic depression

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Results

Conclusion