The laryngeal chemoreflex (LCR) is believed to play an integral role in Sudden Infant Death Syndrome (SIDS). Activation of this reflex results in apnea and bradycardia and can be prolonged by temperature increases in the nucleus of the solitary tract (NTS) in the brainstem. Recent in vivo research has demonstrated that the transient receptor potential vanilloid type 1 receptor (TRPV1) located in the NTS is responsible for the thermal prolongation of the LCR, yet research on TRPV1 at laryngeal afferents is lacking at the synaptic level. It is the goal of this research proposal to investigate TRPV1 in NTS neurons labeled with laryngeal afferents. We will use the anterograde tracer DiA to label the superior laryngeal nerve and then perform whole cell patch clamp recordings from labeled NTS neurons.
Aim 1 will investigate whether TRPV1 can modulate glutamate release at these labeled NTS neurons. This work will determine whether all laryngeal labeled neurons are TRPV1 positive and the different ways this receptor can alter synaptic transmission. These experiments have the potential to provide a synaptic level correlate to the observed in vivo effects of TRPV1 on the LCR. Recent research has shown that nicotine also affects the thermal prolongation of the LCR. Consequently, Aim 2 will examine the potential interaction of nicotine with the TRPV1 modulation of glutamate. Additionally, this aim will also look for the possible role nicotinic acetylcholine receptors play in the modulation of glutamate release to laryngeal labeled NTS neurons. Finally, Aim 3 will investigate whether laryngeal labeled NTS neurons positive for TRPV1 will be primarily GABAergic. Research has determined that an increase in GABA release is responsible for the prolongation of the LCR and this aim will look at whether increased GABA release is through directly driving GABAergic NTS neurons or through activating a polysynaptic circuit to increase GABA. This will be accomplished by performing immunohistochemistry on all our recorded neurons and determine if TRPV1 is selectively located at GABAergic NTS neurons. Potentially through a broader understanding of how TRPV1 works at laryngeal afferents to NTS neurons we might be able to discover new therapeutic strategies for the prevention of SIDS.

Public Health Relevance

Abnormalities in the laryngeal chemoreflex have been implicated in Sudden Infant Death Syndrome. Little is known about the central mechanisms of laryngeal afferent transmission and this project seeks to investigate new ideas about information transfer from the superior laryngeal nerve to the brainstem and the involvement of the transient receptor potential vanilloid type 1 receptor. The results may identify targets useful for future therapeutic strategies to prevent or lower the risk of Sudden Infant Death Syndrome.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Laposky, Aaron D
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Oregon Health and Science University
Schools of Medicine
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Fawley, Jessica A; Hofmann, Mackenzie E; Andresen, Michael C (2016) Distinct Calcium Sources Support Multiple Modes of Synaptic Release from Cranial Sensory Afferents. J Neurosci 36:8957-66
Hofmann, Mackenzie E; Andresen, Michael C (2016) Vanilloids selectively sensitize thermal glutamate release from TRPV1 expressing solitary tract afferents. Neuropharmacology 101:401-11
Fawley, Jessica A; Hofmann, Mackenzie E; Largent-Milnes, Tally M et al. (2015) Temperature differentially facilitates spontaneous but not evoked glutamate release from cranial visceral primary afferents. PLoS One 10:e0127764
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