Capsaicin Enhances Glutamatergic Synaptic Transmission to Neonatal Rat Hypoglossal Motor Neurons via a TRPV1-Independent Mechanism.

Prajwal P Thakre,Mark C Bellingham

doi:10.3389/fncel.2017.00383

Abstract

We investigated whether capsaicin modulated synaptic transmission to hypoglossal motor neurons (HMNs) by acting on transient receptor potential vanilloid type 1 (TRPV1) receptors. Using whole-cell patch clamp recording from neonatal rat HMNs, we found that capsaicin increased spontaneous excitatory post-synaptic current (sEPSC) frequency and amplitude. Interestingly, the only effect of capsaicin on spontaneous inhibitory post-synaptic currents (sIPSCs) was a significant decrease in sIPSC amplitude without altering frequency, indicating a post-synaptic mechanism of action. The frequency of miniature excitatory post-synaptic currents (mEPSCs), recorded in the presence of tetrodotoxin (TTX), was also increased by capsaicin, but capsaicin did not alter mEPSC amplitude, consistent with a pre-synaptic mechanism of action. A negative shift in membrane current (Iholding) was elicited by capsaicin under both recording conditions. The effect of capsaicin on excitatory synaptic transmission remained unchanged in the presence of the TRPV1 antagonists, capsazepine or SB366791, suggesting that capsaicin acts to modulate EPSCs via a mechanism which does not require TRPV1 activation. Capsaicin, however, did not alter evoked excitatory post-synaptic currents (eEPSCs) or the paired-pulse ratio (PPR) of eEPSCs. Repetitive action potential (AP) firing in HMNs was also unaltered by capsaicin, indicating that capsaicin does not change HMN intrinsic excitability. We have demonstrated that capsaicin modulates glutamatergic excitatory, as well as glycinergic inhibitory, synaptic transmission in HMNs by differing pre- and post-synaptic mechanisms. These results expand our understanding regarding the extent to which capsaicin can modulate synaptic transmission to central neurons.

Highlights

Hypoglossal motor neurons (HMNs) innervate tongue muscles and play a critical role in control of oral behaviors like respiration, licking, suckling, mastication and vocalization (Berger et al, 1995)
The key finding of the present study is that capsaicin enhanced the frequency of spontaneous and miniature excitatory synaptic currents to rat HMNs in vitro, but did not alter evoked excitatory synaptic currents, consistent with pre-synaptic enhancement of action potential-independent release probability
We show that capsaicin significantly decreased spontaneous glycinergic inhibitory synaptic current amplitude, but not frequency, consistent with a postsynaptic effect on glycine receptor activity

Summary

Introduction

Hypoglossal motor neurons (HMNs) innervate tongue muscles and play a critical role in control of oral behaviors like respiration, licking, suckling, mastication and vocalization (Berger et al, 1995). Many neuroactive chemicals, including adenosine (Bellingham and Berger, 1994; Funk et al, 1997), acetylcholine (Bellingham and Berger, 1996; Ireland et al, 2012), serotonin (Singer et al, 1996) and noradrenaline (Parkis et al, 1995), can modulate these excitatory inputs to HMNs. The coordination of HMN activity with other upper airway muscles during oral behaviors suggests that visceral and nociceptive afferent feedback are likely to modulate HMNs or their inputs (Fregosi and Ludlow, 2014). Activation of TRPV1 by capsaicin is known to initiate depolarization by the influx of sodium and calcium ions in peripheral sensory nerves, causing action potential generation and propagation to the brainstem and spinal cord, giving rise to burning or itching sensations (Anand and Bley, 2011)

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