Parasympathetic Vagal Neurons Research Articles

Stress-sensitive neural circuits change the gut microbiome via duodenal glands

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner's glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis. Brunner's glands mediated the enrichment of gut Lactobacillus species in response to vagus nerve stimulation. Cell-specific ablation of the glands markedly suppressed Lactobacilli counts and heightened vulnerability to infection. In the forebrain, we mapped a vagally mediated, polysynaptic circuit connecting the central nucleus of the amygdala to Brunner's glands. Chronic stress suppressed central amygdala activity and phenocopied the effects of gland lesions. Conversely, excitation of either the central amygdala or parasympathetic vagal neurons activated Brunner's glands and reversed the effects of stress on the gut microbiome and immunity. The findings revealed a tractable brain-body mechanism linking psychological states to host defense.

Early Denervation and Later Reinnervation of the Heart Following Cardiac Transplantation: A Review.

Heart transplantation (HTx) surgically interrupts the parasympathetic vagal neurons and the intrinsic postganglionic sympathetic nerve fibers traveling from the stellate ganglia to the myocardium, causing axonal Wallerian degeneration and thus extrinsic cardiac denervation.[1][1], [2][2], [3][3], [4

Hypocretin-1 (Orexin-A) Facilitates Inhibitory and Diminishes Excitatory Synaptic Pathways to Cardiac Vagal Neurons in the Nucleus Ambiguus

Hypocretin-1 is a neuropeptide recently shown to be involved in autonomic regulation. Hypocretin-1 is expressed by hypothalamic neurons, which project to many regions of the central nervous system, including the nucleus ambiguus. One possible site of action of hypocretin-1 could be cardioinhibitory parasympathetic vagal neurons within the nucleus ambiguus. This study examines whether hypocretin-1 modulates inhibitory and excitatory postsynaptic currents in cardiac vagal neurons in the rat nucleus ambiguus. GABAergic, glycinergic, and glutamatergic activity to cardiac vagal neurons was examined using whole-cell patch-clamp recordings in an in vitro brain slice preparation. Hypocretin-1 (1 microM) produced a significant increase in the frequency and amplitude of both GABAergic and glycinergic inhibitory postsynaptic currents and a significant decrease in the frequency of glutamatergic excitatory postsynaptic currents. Application of tetrodotoxin (0.5 microM) blocked all of the responses to hypocretin-1, indicating the changes in neurotransmission with hypocretin-1 do not occur at presynaptic terminals but rather occur at the preceding GABAergic, glycinergic, and glutamatergic neurons that project to cardiac vagal neurons. The increase in GABAergic and glycinergic inhibitory postsynaptic currents, and the decrease in glutamatergic excitatory postsynaptic currents, could be mechanisms by which hypocretin-1 affects heart rate and cardiac function.

Fentanyl inhibits GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

Fentanyl citrate is a synthetic opiate analgesic often used clinically for neonatal anesthesia. Although fentanyl significantly depresses heart rate, the mechanism of inducing bradycardia remains unclear. One possible site of action is the cardioinhibitory parasympathetic vagal neurons in the nucleus ambiguus (NA), from which originates control of heart rate and cardiac function. Inhibitory synaptic activity to cardiac vagal neurons is a major determinant of their activity. Therefore, the effect of fentanyl on GABAergic neurotransmission to parasympathetic cardiac vagal neurons was studied using whole-cell patch clamp electrophysiology. Application of fentanyl induced a reduction in both the frequency and amplitude of GABAergic IPSCs in cardiac vagal neurons. This inhibition was mediated at both pre- and postsynaptic sites as evidenced by a dual decrease in the frequency and amplitude of spontaneous miniature IPSCs. Application of the selective μ-antagonist CTOP abolished the fentanyl-mediated inhibition of GABAergic IPSCs. These results demonstrate that fentanyl acts on μ-opioid receptors on cardiac vagal neurons and neurons preceding them to reduce GABAergic neurotransmission and increase parasympathetic activity. The inhibition of GABAergic effects may be one mechanism by which fentanyl induces bradycardia.

Three types of postsynaptic glutamatergic receptors are activated in DMNX neurons upon stimulation of NTS.

While it is widely accepted that parasympathetic activity plays a significant role in cardiovascular, bronchomotor, and gastrointestinal function, little is known about the synaptic control of parasympathetic vagal neurons. In this study, we identified the neurotransmitter(s) and postsynaptic responses in dorsal motor nucleus of the vagus (DMNX) neurons upon stimulation of the nucleus of the solitary tract (NTS). Neurons were visualized in rat brain stem slices, and perforated patch-clamp techniques were used to record postsynaptic currents. NTS stimulation activated glutamatergic currents in DMNX that were separated into N-methyl-D-aspartate (NMDA) and non-NMDA components using D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. The non-NMDA component was further characterized using cyclothiazide and concanavalin A to block desensitization of DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and kainate receptors, respectively. Cyclothiazide increased the postsynaptic amplitude, whereas concanavalin A augmented duration, suggesting kainate, but not AMPA, currents are curtailed by desensitization. High frequency stimulations did not alter synaptic efficacy. In conclusion, this study demonstrates the existence of a monosynaptic glutamatergic pathway from NTS that activates NMDA, kainate, and AMPA postsynaptic receptors in DMNX neurons.

Acetylcholine activates a nicotinic receptor and an inward current in dorsal motor nucleus of the vagus neurons in vitro

This study examines the effect of acetylcholine (Ach) on parasympathetic vagal neurons in the dorsal motor nucleus of the vagus (DMNX). Patch-clamp techniques were utilized to examine voltage and ligand-gated currents in visualized DMNX neurons in an in-vitro slice. Ach (100 μM) activated an inward current, −196.4 ± 56.9 pA at −80 mV ( n = 15) that was accompanied by a decrease in membrane resistance of 48.6 ± 9.2% in a population of DMNX neurons. The reversal potential for this ligand-gated current was −11.3 ± 11.5 mV. The specific agonist nicotine (200 μM) elicited similar responses. Nicotine decreased membrane resistance by 60.9 ± 4.3% and activated an inward current (−215.7 ± 45.7 pA at −80 mV) that reversed at −12.7 ± 20.4 mV ( n = 16). Bethanecol (100 μM), a specific muscarinic agonist, had no effect. Neither Ach or nicotine had any effect on the voltage-gated sodium and outward potassium currents present in these neurons.