NEUROTRANSMITTERS AND VISCERAL SENSORY NEURONS

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Visceral sensory neurons of the nodose ganglion innervate major organ systems of the thorax and abdomen, and are an integral part of visceral reflexes involved in maintaining homeostasis. These placode-derived visceral sensory neurons contains multiple neuropeptides and putative neurotransmitter, the content of which is not static. However, little is known about the epidgetic influences on the expression of neuropeptides and neurotransmitter enzymes in mature nodose ganglion neurons. The proposed studies will determine the roles of transported factors and depolarizing signals on the regulation of specific neuropeptides and neurotransmitter enzymes in these neurons. Our initial studies will further clarify the neurochemical identifies and plasticity of nodose ganglion neurons both in situ and in vitro. A tissue culture paradigm will be used to evaluate changes in neuropeptide and neurotransmitter enzyme mRNAs in individual neurons resulting from both loss of target contact and changes in depolarizing influences. We propose that the target-derived regulatory agents involved in modulating neuropeptide and neurotransmitter enzymes mRNA expression include specific retrogradely-transported neurotrophins. Because placeode- derived neurons are responsive t other neurotrophins, brain derived neurotrophic factor (BDNF) and neurothrophisn involved in regulation of mature neuronal phenotypes of nodose ganglion neurons are primarily BDNF and NT-3. A second set of studies will determine which member(s) of the TrK family of neurotrophin receptors is(are) associated with nodose ganglion neurons that their relationship with specific neurochemically- defined neurons. The retrograde transport of specific neurotrophins (NGF, BDFN, NT-3) in nodose ganglion neurons will also be evaluated. A final group of studies will determine the role of NGF, BDNF and/or NT-3 nodose ganglion neurons in vivo and in vitro. These visceral sensory neurons are critical for visceral homeostasis, and relate to the many pathologies of visceral regulation (e.g. hypertension, pulmonary dysfunction, gastrointestinal disorders). Understanding the regulation of neuropeptides and neurotransmitter enzymes expression by these neurons is important in understanding, and ultimately manipulating, their patterns of chemical neuron-transmission under various conditions and pathologies. Likewise, knowledge of neurotrophin actions in a placode- derived population of sensory neurons will provide a greater understanding of neurotrophic actions as therapeutic agents in a variety of disorders.