CHANNELING SATIATION AT THE ST-NTS SYNAPSE: THE ROLES OF TRP CHANNELS

Shaw-wen Wu

Vagal afferent neurons relay meal-related signals from the gut to the hindbrain nucleus of the solitary tract (NTS) providing key controls of feeding and gastrointestinal reflexes. Centrally, vagal afferents form strong excitatory synapses with NTS neurons and release glutamate via three distinct processes; synchronous, asynchronous, and spontaneous. Transient Receptor Potential (TRP) ion channels expressed on vagal afferent terminals control specific forms of glutamate release and determine the nature of information transfer. This dissertation further explores the contributions of TRP channels to vagal afferent signaling. Results from previous work and in Chapter One, reveal that while TRPV1 contributes to control of quantal forms of glutamate release, the absence of TRPV1 only incompletely diminishes asynchronous release, while temperature sensitive spontaneous release is preserved. From these findings we concluded that additional TRP channels contribute to these forms of glutamate release and established criteria to identify additional TRP channel contributions. In Chapter Two, we identify and characterize the contribution of TRPV3 vagal afferent signaling. We determined that TRPV3 was present in vagal afferent neurons in very low abundance. Furthermore, we showed that FPP was a selective agonist for TRPV3 in primary nodose neurons compared to ethyl vanillin (EVA) and Eugenol, both of which we showed to be non-selective TRPV3 agonists. While low in abundance, TRPV3 appeared to enhance sensitivity to other TRP agonists. In Chapter Three, we focused on TRPA1 and observed that TRPA1 is expressed in high abundance and makes strong contributions to glutamate release from vagal afferent neurons. Furthermore, we discovered that EVA, a reported TRPV3 agonist, is actually a selective TRPA1 agonist. These observations are reported in Chapter Four in which we compare and contrast channel activation by EVA and allyl isothiocyanate (AITC), a common and selective agonist for TRPA1. In Chapters Three and Four we also show that TRPA1 not only co-expresses with TRPV1 but interacts with TRPV1 within native tissues. Collectively, these findings describe contributions of TRPV3 and TRPA1 in vagal afferent signaling and suggest their importance in the satiety control and other autonomic reflex pathways.

CHANNELING SATIATION AT THE ST-NTS SYNAPSE: THE ROLES OF TRP CHANNELS

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