scholarly journals Effects of cholecystokinin-8s in the nucleus tractus solitarius of vagally deafferented rats

2007 ◽  
Vol 292 (3) ◽  
pp. R1092-R1100 ◽  
Author(s):  
V. Baptista ◽  
K. N. Browning ◽  
R. A. Travagli

We have shown recently that cholecystokinin octapeptide (CCK-8s) increases glutamate release from nerve terminals onto neurons of the nucleus tractus solitarius pars centralis (cNTS). The effects of CCK on gastrointestinal-related functions have, however, been attributed almost exclusively to its paracrine action on vagal afferent fibers. Because it has been reported that systemic or perivagal capsaicin pretreatment abolishes the effects of CCK, the aim of the present work was to investigate the response of cNTS neurons to CCK-8s in vagally deafferented rats. In surgically deafferented rats, intraperitoneal administration of 1 or 3 μg/kg CCK-8s increased c-Fos expression in cNTS neurons (139 and 251% of control, respectively), suggesting that CCK-8s' effects are partially independent of vagal afferent fibers. Using whole cell patch-clamp techniques in thin brain stem slices, we observed that CCK-8s increased the frequency of spontaneous and miniature excitatory postsynaptic currents in 43% of the cNTS neurons via a presynaptic mechanism. In slices from deafferented rats, the percentage of cNTS neurons receiving glutamatergic inputs responding to CCK-8s decreased by ∼50%, further suggesting that central terminals of vagal afferent fibers are not the sole site for the action of CCK-8s in the brain stem. Taken together, our data suggest that the sites of action of CCK-8s include the brain stem, and in cNTS, the actions of CCK-8s are not restricted to vagal central terminals but that nonvagal synapses are also involved.

1990 ◽  
Vol 258 (2) ◽  
pp. G320-G327 ◽  
Author(s):  
William D. Barber ◽  
Chun-Su Yuan ◽  
Brian J. Cammarata

Gastric vagal fibers on the proximal stomach that join the dorsal and ventral vagal trunks were electrically stimulated to localize and evaluate brain stem neuronal interactions in anesthetized cats. The brain stem responses were located in nucleus tractus solitarius in the dorsomedial, caudal region of the medulla oblongata. There was no significant difference in the mean latency of the gastric vagally evoked brain stem response between the dorsal and ventral vagal trunks. The responses consisted of single or multiple spikes with a mean latency of ap290 ± 50 (SD) ms. Forty-one percent, or 168 unitary responses of the 406 total responses recorded, showed convergence of proximal gastric vagal input from both the dorsal and ventral vagal trunks on the same recording site or on the same cell. Of those unitary responses that received convergent proximal gastric vagal input, 95 unitary responses (57%) showed convergence of input to the same area, on different cells at the same recording site during a single trial. Seventy-three single units (43%) received convergent input from proximal gastric vagal afferent fibers in both the dorsal and ventral trunks. Fifty-two, or 7l%, of the single unit convergent responses were excitatory in nature, whereas the remaining 29% were inhibitory. These data demonstrated that proximal gastric vagal afferent fibers that join the dorsal and ventral trunks converged on a significant number of single neurons in the brain stem. The convergent response was synaptically secure and exerted an identifiable biasing effect on the response of the brain stem neuron. These convergent interactions may play an important role in reflex mechanisms concerned with adaptive relaxation to accommodate the ingested content by the proximal stomach. gastric; proximal gastric vagal; ventral vagus; dorsal vagus; nucleus tractus solitarius; vagal brain stem interactions Submitted on March 14, 1988 Accepted on September 19, 1989


2011 ◽  
Vol 301 (2) ◽  
pp. R394-R401 ◽  
Author(s):  
Kirsteen N. Browning ◽  
ShuXia Wan ◽  
Vander Baptista ◽  
R. Alberto Travagli

Baroreceptor inputs to nucleus of the tractus solitarius medialis (mNTS) neurons can be differentiated, among other features, by their response to vanilloid or purinergic agonists, active only on C- or A-fibers, respectively. A major aim of this study was to examine whether neurons of NTS centralis (cNTS), a subnucleus dominated by esophageal inputs, exhibit a similar dichotomy. Since it has been suggested that cholecystokinin (CCK), exerts its gastrointestinal (GI)-related effects via paracrine activation of vagal afferent C-fibers, we tested whether CCK-sensitive fibers impinging upon cNTS neurons are responsive to vanilloid but not purinergic agonists. Using whole cell patch-clamp recordings from cNTS, we recorded miniature excitatory postsynaptic currents (mEPSCs) to test the effects of the vanilloid agonist capsaicin, the purinergic agonist α,β-methylene-ATP (α,β-Met-ATP), and/or CCK-octapeptide (CCK-8s). α,β-Met-ATP, capsaicin; and CCK-8s increased EPSC frequency in 37, 71, and 46% of cNTS neurons, respectively. Approximately 30% of cNTS neurons were responsive to both CCK-8s and α,β-Met-ATP, to CCK-8s and capsaicin, or to α,β-Met-ATP and capsaicin, while 32% of neurons were responsive to all three agonists. All neurons responding to either α,β-Met-ATP or CCK-8s were also responsive to capsaicin. Perivagal capsaicin, which is supposed to induce a selective degeneration of C-fibers, decreased the number of cNTS neurons responding to capsaicin or CCK-8s but not those responding to α,β-Met-ATP. In summary, GI inputs to cNTS neurons cannot be distinguished on the basis of their selective responses to α,β-Met-ATP or capsaicin. Our data also indicate that CCK-8s increases glutamate release from purinergic and vanilloid responsive fibers impinging on cNTS neurons.


1983 ◽  
Vol 50 (4) ◽  
pp. 743-769 ◽  
Author(s):  
P. Rudomin ◽  
I. Jimenez ◽  
M. Solodkin ◽  
S. Duenas

The present series of investigations was aimed to disclose the possible sites of action of excitatory and inhibitory inputs on tho-interneuron pathway mediating the primary afferent depolarization (PAD) of group I afferents of extensor muscles in the cat spinal cord. To this end we compared the effects produced by stimulation of segmental and descending pathways on the PAD generated either by stimulation of group I fibers of flexor muscles or by intraspinal microstimulation. It was assumed that under the appropriate conditions the PAD produced by intraspinal microstimulation results from the activation of the last-order interneurons in the PAD pathway and may, therefore, allow detection pathway. The PAD of single group I afferent fibers was determined in barbiturate-anesthetized preparations by measuring the test stimulus current required to maintain a constant probability of antidromic firing. This was achieved by means of a feedback system that continuously adjusted the test stimulus current to the required values. The PAD of individual group Ia gastrocnemius soleus (GS) fibers that is produced by activation of the low-threshold afferents of the posterior biceps and semitendinosus nerve was found to be inhibited by conditioning stimulation of the relatively low-threshold cutaneous fibers and also by stimulation of supraspinal structures such as the ipsilateral brain stem reticular formation, the contralateral red nucleus, and the contralateral pyramidal tract. In contrast, the PAD of group Ia fibers produced by microstimulation applied in the intermediate nucleus could be inhibited only by stimulation of the brain stem reticular formation but not by stimulation of the other descending inputs presently tested or by stimulation of cutaneous nerves. PAD of group Ia fibers was produced also by microstimulation applied within the motor nucleus. However, in most fibers the resulting PAD could not be inhibited either by stimulation of the brain stem reticular formation, the red nucleus, the pyramidal tract, or cutaneous nerves. Stimulation of cutaneous and of flexor muscle nerves of the brain stem reticular formation, the red nucleus, and the pyramidal tract all produced PAD of the group Ib GS fibers.(ABSTRACT TRUNCATED AT 400 WORDS)


1989 ◽  
Vol 257 (1) ◽  
pp. G24-G29
Author(s):  
W. D. Barber ◽  
C. S. Yuan

The brain stem neuronal responses to electrical stimulation of gastric branches of the ventral vagal trunk serving the proximal stomach were localized and evaluated in anesthetized cats. The responses were equally distributed bilaterally in the region of nucleus solitarius in the caudal brain stem. The mean latency of the response was 289 +/- 46 (SD) ms, which translated into a conduction velocity of less than 1 m/s based on the distance between the stimulating and recording electrodes. The responses consisted of single and multiple spikes that showed slight variability in the latency, indicating orthodromic activation via a synapse in approximately 98% of the responses recorded. Forty two percent of the units tested showed evidence of convergence of input from vagal afferent fibers in different branches of the ventral vagal trunk that served the proximal stomach. The resultant activity pattern of the unitary response appeared to be the product of 1) the gastric sensory input or modality conveyed by the afferent source and 2) the time of arrival and diversity of modalities served by other gastric afferents impinging on the unit. This provides a mechanism capable of responding on the basis of specific sensory modalities that dynamically reflect ongoing events monitored and conveyed by other gastric afferents in the region.


2005 ◽  
Vol 94 (4) ◽  
pp. 2763-2771 ◽  
Author(s):  
V. Baptista ◽  
Z. L. Zheng ◽  
F. H. Coleman ◽  
R. C. Rogers ◽  
R. A. Travagli

Cholecystokinin (CCK) is released from enteroendocrine cells after ingestion of nutrients and induces multiple effects along the gastrointestinal tract, including gastric relaxation and short-term satiety. We used whole cell patch-clamp and immunohistochemical techniques in rat brain stem slices to characterize the effects of CCK. In 45% of the neurons of nucleus tractus solitarius subnucleus centralis (cNTS), perfusion with the sulfated form of CCK (CCK-8s) increased the frequency of spontaneous excitatory currents (sEPSCs) in a concentration-dependent manner (1–300 nM). The threshold for the CCK-8s excitatory effect was 1 nM, the EC50 was 20 nM, and Emax was 100 nM. The excitatory effects of CCK-8s were still present when the slices were preincubated with tetrodotoxin or bicuculline or when the recordings were conducted with Cs+ electrodes. Pretreatment with the CCK-A receptor antagonist, lorglumide (1 μM), antagonized the effects of CCK-8s, whereas perfusion with the CCK-B preferring agonist CCK-8 nonsulfated (CCK-ns, 1 μM) did not affect the frequency of sEPSCs. Similarly, pretreatment with the CCK-B receptor antagonist, triglumide (1 μM), did not prevent the actions of CCK-8s. Although the majority (i.e., 76%) of CCK-8s unresponsive cNTS neurons had a bipolar somata shape and were TH-IR negative, no differences were found in either the morphological or the neurochemical phenotype of cNTS neurons responsive to CCK-8s. Our results suggest that the excitatory effects of CCK-8s on terminals impinging on a subpopulation of cNTS neurons are mediated by CCK-A receptors; these responsive neurons, however, do not have morphological or neurochemical characteristics that automatically distinguish them from nonresponsive neurons.


2020 ◽  
Vol 319 (6) ◽  
pp. C1097-C1106
Author(s):  
Forrest J. Ragozzino ◽  
Rachel A. Arnold ◽  
Cody W. Kowalski ◽  
Marina I. Savenkova ◽  
Ilia N. Karatsoreos ◽  
...  

Circulating blood glucocorticoid levels are dynamic and responsive to stimuli that impact autonomic function. In the brain stem, vagal afferent terminals release the excitatory neurotransmitter glutamate to neurons in the nucleus of the solitary tract (NTS). Vagal afferents integrate direct visceral signals and circulating hormones with ongoing NTS activity to control autonomic function and behavior. Here, we investigated the effects of corticosterone (CORT) on glutamate signaling in the NTS using patch-clamp electrophysiology on brain stem slices containing the NTS and central afferent terminals from male C57BL/6 mice. We found that CORT rapidly decreased both action potential-evoked and spontaneous glutamate signaling. The effects of CORT were phenocopied by dexamethasone and blocked by mifepristone, consistent with glucocorticoid receptor (GR)-mediated signaling. While mRNA for GR was present in both the NTS and vagal afferent neurons, selective intracellular quenching of G protein signaling in postsynaptic NTS neurons eliminated the effects of CORT. We then investigated the contribution of retrograde endocannabinoid signaling, which has been reported to transduce nongenomic GR effects. Pharmacological or genetic elimination of the cannabinoid type 1 receptor signaling blocked CORT suppression of glutamate release. Together, our results detail a mechanism, whereby the NTS integrates endocrine CORT signals with fast neurotransmission to control autonomic reflex pathways.


1985 ◽  
Vol 369 (1) ◽  
pp. 1-15 ◽  
Author(s):  
J A Bennett ◽  
C S Goodchild ◽  
C Kidd ◽  
P N McWilliam
Keyword(s):  

1995 ◽  
Vol 268 (5) ◽  
pp. R1327-R1331 ◽  
Author(s):  
S. Laye ◽  
R. M. Bluthe ◽  
S. Kent ◽  
C. Combe ◽  
C. Medina ◽  
...  

To test the possibility that the vagus nerve is involved in the communication between the immune system and the brain, we injected sham-operated and vagotomized mice with physiological saline or lipopolysaccharide (LPS; 400 micrograms/kg ip). Vagotomy attenuated LPS-induced depression of general activity measured 2 h after treatment but did not alter the increase in plasma levels of IL-1 beta in response to LPS. In addition, vagotomy abrogated the LPS-induced increase in the levels of transcripts for IL-1 beta, as determined by semiquantitative polymerase chain reaction after reverse transcription, in the hypothalamus and hippocampus, but not in the pituitary of vagotomized mice. This relationship between the effects of vagotomy on the behavioral effects of LPS and the LPS-induced brain expression of IL-1 beta mRNA indicates that vagal afferent fibers play a prominent role in the pathways of communication between the immune system and the brain.


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