Peptide and Lipid Modulation of Glutamatergic Afferent Synaptic Transmission in the Solitary Tract Nucleus

Abstract

The brainstem nucleus of the solitary tract (NTS) holds the first central neurons in major homeostatic reflex pathways. These homeostatic reflexes regulate and coordinate multiple organ systems from gastrointestinal to cardiopulmonary functions. The core of many of these pathways arise from cranial visceral afferent neurons that enter the brain as the solitary tract (ST) with more than two-thirds arising from the gastrointestinal system. About one quarter of ST afferents have myelinated axons but the majority are classed as unmyelinated C-fibers. All ST afferents release the fast neurotransmitter glutamate with remarkably similar, high-probability release characteristics. Second order NTS neurons receive surprisingly limited primary afferent information with one or two individual inputs converging on single second order NTS neurons. A- and C-fiber afferents never mix at NTS second order neurons. Many transmitters modify the basic glutamatergic excitatory postsynaptic current often by reducing glutamate release or interrupting terminal depolarization. Thus, a distinguishing feature of ST transmission is presynaptic expression of G-protein coupled receptors for peptides common to peripheral or forebrain (e.g., hypothalamus) neuron sources. Presynaptic receptors for angiotensin (AT1), vasopressin (V1a), oxytocin, opioid (MOR), ghrelin (GHSR1), and cholecystokinin differentially control glutamate release on particular subsets of neurons with most other ST afferents unaffected. Lastly, lipid-like signals are transduced by two key ST presynaptic receptors, the transient receptor potential vanilloid type 1 and the cannabinoid receptor that oppositely control glutamate release. Increasing evidence suggests that peripheral nervous signaling mechanisms are repurposed at central terminals to control excitation and are major sites of signal integration of peripheral and central inputs particularly from the hypothalamus.

Vagal Sensory Neuron Subtypes that Differentially Control Breathing

“…The axons of vagal sensory neurons densely innervate the NTS, area postrema, and spinal trigeminal nucleus (Berthoud and Neuhuber, 2000; Kalia and Mesulam, 1980), and topographic organization of vagal inputs in the NTS based on either physiological function or organ innervation has been proposed (Altschuler et al, 1989; Bailey et al, 2006; Katz and Karten, 1983; Kubin et al, 2006), but debated (Andresen et al, 2012). Here, we used genetically encoded neural tracers to ask how inputs from P2ry1 and Npy2r neurons are organized centrally.…”

Role of the dorsomedial medulla in suppression of cough by codeine in cats

“…Codeine and other agonists of μ-opioid receptors may mediate neuronal inhibition in the several subdivisions of the NTS (Poole et al, 2007) by both pre- and post-synaptic mechanisms (Endoh, 2006; Ohi et al, 2007; Boxwell et al, 2013) including modulation of glutamatergic neurotransmission (Andresen et al, 2013) and local GABA activity (Herman et al, 2012). The antitussive activity of codeine in cat is likely mediated also via non-opioid receptor mechanisms (Nosalova, 1998; for the discussion see Poliacek et al, 2010).…”

Frequency‐dependent facilitation of synaptic throughput via postsynaptic NMDA receptors in the nucleus of the solitary tract

“…Electrophysiological experiments have clearly established that AMPA‐R activation following vagal afferent stimulation triggers fast excitatory postsynaptic currents (EPSCs) in NTS neurons (Andresen et al . ). Moreover, there is abundant evidence that AMPA‐R EPSCs critically contribute to synaptic transmission and successful generation of action potentials (APs) in NTS neurons (Bailey et al .…”

“…Glutamate acts at both 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA)-and N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptors (Aicher et al 1999;Lachamp et al 2003;Antunes et al 2004;Almado & Machado, 2005;Mutolo et al 2007;Sartor & Verberne, 2007;Balland et al 2008;Liu et al 2012;Marques-Lopes et al 2012). Electrophysiological experiments have clearly established that AMPA-R activation following vagal afferent stimulation triggers fast excitatory postsynaptic currents (EPSCs) in NTS neurons (Andresen et al 2012). Moreover, there is abundant evidence that AMPA-R EPSCs critically contribute to synaptic transmission and successful generation of action potentials (APs) in NTS neurons (Bailey et al 2006;Appleyard et al 2007;Peters et al 2010).…”