scholarly journals Dexamethasone Rapidly Increases GABA Release in the Dorsal Motor Nucleus of the Vagus via Retrograde Messenger-Mediated Enhancement of TRPV1 Activity

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e70505 ◽  
Author(s):  
Andrei V. Derbenev ◽  
Bret N. Smith
2010 ◽  
Vol 103 (2) ◽  
pp. 904-914 ◽  
Author(s):  
Hong Gao ◽  
Bret N. Smith

Type A γ-aminobutyric acid (GABAA) receptors expressed in the dorsal motor nucleus of vagus (DMV) critically regulate the activity of vagal motor neurons and, by inference, the gastrointestinal (GI) tract. Two types of GABAA receptor-mediated inhibition have been identified in the brain, represented by phasic ( Iphasic) and tonic ( Itonic) inhibitory currents. The hypothesis that Itonic regulates neuron activity was tested in the DMV using whole cell patch-clamp recordings in transverse brain stem slices from rats. An Itonic was present in a subset of DMV neurons, which was determined to be mediated by different receptors than those mediating fast, synaptic currents. Preapplication of tetrodotoxin significantly decreased the resting Itonic amplitude in DMV neurons, suggesting that most of the current was due to action potential (AP)–dependent GABA release. Blocking GABA transport enhanced Itonic and multiple GABA transporters cooperated to regulate Itonic. The Itonic was composed of both a gabazine-insensitive component that was nearly saturated under basal conditions and a gabazine-sensitive component that was activated when extracellular GABA concentration was elevated. Perfusion of THIP (10 μM) significantly increased Itonic amplitude without increasing Iphasic amplitude. The Itonic played a major role in determining the overall excitability of DMV neurons by contributing to resting membrane potential and AP frequency. Our results indicate that Itonic contributes to DMV neuron membrane potential and activity and is thus an important regulator of vagally mediated GI function.


2012 ◽  
Vol 108 (5) ◽  
pp. 1484-1491 ◽  
Author(s):  
Eva C. Bach ◽  
Bret N. Smith

Activity of neurons in the dorsal motor nucleus of the vagus nerve (DMV) is closely regulated by synaptic input, and regulation of that input by glutamate receptors on presynaptic terminals has been proposed. Presynaptic N-methyl-d-aspartic acid (NMDA) receptors have been identified in a number of brain regions and act to modulate neurotransmitter release, but functional presynaptic NMDA receptors have not been adequately studied in the DMV. This study identified the presence and physiological function of presynaptic NMDA receptors on synaptic input to DMV neurons. Whole-cell patch-clamp recordings from DMV neurons in acute slices from mice revealed prevalent miniature excitatory postsynaptic currents, which were significantly increased in frequency, but not amplitude, by application of NMDA. Antagonism of NMDA receptors with dl-2-amino-5-phosphonopentanoic acid (100 μM) resulted in a decrease in miniature excitatory postsynaptic current frequency and an increase in the paired pulse ratio of responses following afferent stimulation. No consistent effects of presynaptic NMDA receptor modulation were observed on GABAergic inputs. These results suggest that presynaptic NMDA receptors are present in the dorsal vagal complex and function to facilitate the release of glutamate, preferentially onto DMV neurons tonically, with little effect on GABA release. This type of presynaptic modulation represents a potentially novel form of glutamate regulation in the DMV, which may function to regulate glutamate-induced activity of central parasympathetic circuits.


Neuroscience ◽  
1997 ◽  
Vol 79 (3) ◽  
pp. 671-681 ◽  
Author(s):  
M Bertolino ◽  
K.J Kellar ◽  
S Vicini ◽  
R.A Gillis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Xinyan Gao ◽  
Yongfa Qiao ◽  
Baohui Jia ◽  
Xianghong Jing ◽  
Bin Cheng ◽  
...  

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynapticμ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.


Neurology ◽  
2006 ◽  
Vol 66 (7) ◽  
pp. 1100-1102 ◽  
Author(s):  
K. J. Klos ◽  
J. E. Ahlskog ◽  
K. A. Josephs ◽  
H. Apaydin ◽  
J. E. Parisi ◽  
...  

The authors assessed the frequency of spinal cord α-synuclein pathology in neurologically asymptomatic individuals older than 60 years of age (N = 106). Using α-synuclein immunohistochemistry, nine cases (8%) had incidental Lewy neurites in the intermediolateral column and at least some α-synuclein pathology in the dorsal motor nucleus of the vagus, locus ceruleus, and central raphe nucleus. Sparse α-synuclein pathology was also detected in the substantia nigra, basal forebrain, amygdala, or cortex in all but two cases.


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