Abstract
The nucleus of the solitary tract (NTS) receives visceral information via the solitary tract (ST) that comprises the sensory components of the cranial nerves VII, IX and X. The Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels are non-selective cation channels that are expressed primarily in pain-related sensory neurons and nerve fibers. Thus, TRPA1 expressed in the primary sensory afferents may modulate the function of second order NTS neurons. This hypothesis was tested and confirmed in the present study using acute brainstem slices and caudal NTS neurons by RT-PCR, immunostaining and patch-clamp electrophysiology. The expression of TRPA1 was detected in presynaptic locations, but not the somata of caudal NTS neurons that did not express TRPA1 mRNA or proteins. Moreover, caudal NTS neurons did not show somatodendritic responsiveness to TRPA1 agonists, while TRPA1 immunostaining was detected only in the afferent fibers. Electrophysiological recordings detected activation of presynaptic TRPA1 in glutamatergic terminals synapsing on caudal NTS neurons evidenced by the enhanced glutamatergic synaptic neurotransmission in the presence of TRPA1 agonists. The requirement of TRPA1 for modulation of spontaneous synaptic activity was confirmed using TRPA1 knockout mice where TRPA1 agonists failed to alter synaptic efficacy. Thus, this study provides the first evidence of the TRPA1-dependent modulation of the primary afferent inputs to the caudal NTS. These results suggest that the second order caudal NTS neurons act as a TRPA1-dependent interface for visceral noxious-innocuous integration at the level of the caudal brainstem.
Highlights
The brainstem nucleus of the solitary tract (NTS) is the key integrating relay in the central processing of sensory information from the thoracic and most subdiaphragmatic viscera [1–3]
While glutamate is the major excitatory neurotransmitter in the brainstem, synaptic transmission at the level of the NTS can be modulated via the activation of multiple types of presynaptic ligand-gated ion channels such as transient receptor potential (TRP) channels [15–20]
PresynapNtiTcSEnxepurroesnss.ioOnuor ffiTndRinPgAs1suigngtehstetChaatuthdealseNcoTnSd order caudal NTS neurons act as a TRP ankyrin 1 (TRPA1)
Summary
The brainstem nucleus of the solitary tract (NTS) is the key integrating relay in the central processing of sensory information from the thoracic and most subdiaphragmatic viscera [1–3]. CItenistrianttieorne-sdtienpgentodennottme tahnantesrt(imcounltartoilo,n0.o68f 7T7R±P0V.116s3i,gnni=fi1c2a;n1t0ly[0] iμnMhi,b0i.t7e7d0t±he0.0ev60o,kned= r1e0s;p2o0n0sμesMa,s0r.7ep±o0r.t0e8d6b, yn P=e4t;e5r0s0etμaMl.,, 200.51107[4±60]..0T51h,end=iff7e,rpen
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