Projection target‐specific action of nicotine in the caudal nucleus of the solitary tract

Abstract

The brainstem nucleus of the solitary tract (NTS) is the key integrating relay in the central processing of sensory information from the thoracic and from most subdiaphragmatic viscera. Modulation of neuronal excitability and synaptic activity in the NTS by nicotinic agents can have potent effects on vital physiological functions, such as feeding, digestion, respiration, and blood circulation. Caudal NTS neurons demonstrate considerable heterogeneity in projection targets, synaptic properties, and expression of nicotinic acetylcholine receptors (nAChRs). However, despite its heterogeneity, the caudal NTS may contain discrete subsets of neurons with unique projection target-specific properties. To test this hypothesis, we used in vivo fluorescent tracing and ex vivo patch-clamp electrophysiology to evaluate responsiveness to nicotine of anatomically identified caudal NTS neurons that project to the hypothalamic paraventricular nucleus (PVN) and the brainstem caudal ventrolateral medulla (CVLM). The results of this study demonstrate that responsiveness to nicotine correlates with where the neurons project. Specifically, PVN-projecting caudal NTS neurons respond to nicotine only presynaptically (i.e., via activation of presynaptic nAChRs and potentiation of synaptic release of glutamate), suggesting indirect, glutamate-dependent effects of nicotine on the PVN-projecting NTS circuitry. By contrast, CVLM-projecting caudal NTS neurons exhibit only limited presynaptic, but dominant somatodendritic, responsiveness to nicotine, suggesting that the effects of nicotine on the CVLM-projecting NTS circuitry are direct and largely glutamate independent. Understanding the relationships among function-specific brainstem/hypothalamic neuronal networks, nuclei, and individual neurons could help develop therapies targeting identifiable neuronal circuits to offset impaired autonomic homeostasis.

Effects of acetylcholine and cholinergic antagonists on the activity of nucleus of the solitary tract neurons

“…These studies demonstrated that in the cNTS nicotine application can activate cNTS neurons either by increasing glutamatergic synaptic release, or by direct somatodendritic activation. In addition, it seems that depending on the cNTS projection area of the brain, the responsiveness to nicotine is pre-or post-synaptically mediated (Feng et al, 2012;Feng and Uteshev, 2014). Thus, the present and previous studies (Feng et al, 2012;Feng and Uteshev, 2014;Kalappa et al, 2011), reiterate the role of nicotinic receptors in the cNTS in mediating the effects of ACh in the cNTS.…”

“…In addition, it seems that depending on the cNTS projection area of the brain, the responsiveness to nicotine is pre-or post-synaptically mediated (Feng et al, 2012;Feng and Uteshev, 2014). Thus, the present and previous studies (Feng et al, 2012;Feng and Uteshev, 2014;Kalappa et al, 2011), reiterate the role of nicotinic receptors in the cNTS in mediating the effects of ACh in the cNTS. The present study does not however clarify whether such effects are a consequence of presynaptic of somatodendritic actions of ACh.…”

“…Functional studies have demonstrated pre-and post-synaptic nicotinic receptors (Feng et al, 2012;Feng and Uteshev, 2014;Kalappa et al, 2011) in the cNTS. These studies demonstrated that in the cNTS nicotine application can activate cNTS neurons either by increasing glutamatergic synaptic release, or by direct somatodendritic activation.…”

Effects of acute and chronic nicotine on catecholamine neurons of the nucleus of the solitary tract

“…Nicotine increases vagal afferent discharge and increases the probability of glutamate release from afferent terminals within the NTS (48). It also induces a postsynaptic current in a subpopulation of NTS neurons (27,28,48,96). Nicotine has been shown to activate GABAergic NTS neurons (101), however, the other phenotypes of NTS neurons activated by nicotine are not known.…”

Expression and Function of Transient Receptor Potential Ankyrin 1 Ion Channels in the Caudal Nucleus of the Solitary Tract

“…The ST relays information to the NTS from sensory receptors of the visceral organs and other tissues [4,5,6,7,8,9]. The NTS is a highly heterogeneous population of neurons, where seemingly indistinguishable neighboring neurons could participate in very different autonomic (e.g., gastrointestinal and cardiorespiratory reflexes) and nociceptive functions [8,10,11,12,13,14].…”