Chemical Activation of Cervical Cell Bodies: Effects on Responses to Colorectal Distension in Lumbosacral Spinal Cord of Rats

1999 ◽  
Vol 82 (6) ◽  
pp. 3423-3433 ◽  
Author(s):  
Chao Qin ◽  
Margaret J. Chandler ◽  
Kenneth E. Miller ◽  
Robert D. Foreman

We have shown that stimulation of cardiopulmonary sympathetic afferent fibers activates relays in upper cervical segments to suppress activity of lumbosacral spinal cells. The purpose of this study was to determine if chemical excitation (glutamate) of upper cervical cell bodies changes the spontaneous activity and evoked responses of lumbosacral spinal cells to colorectal distension (CRD). Extracellular potentials were recorded in pentobarbital-anesthetized male rats. CRD (80 mmHg) was produced by inflating a balloon inserted in the descending colon and rectum. A total of 135 cells in the lumbosacral segments (L6–S2) were activated by CRD. Seventy-five percent (95/126) of tested cells received convergent somatic input from the scrotum, perianal region, hindlimb, and tail; 99/135 (73%) cells were excited or excited/inhibited by CRD; and 36 (27%) cells were inhibited or inhibited/excited by CRD. A glutamate (1 M) pledget placed on the surface of C1–C2 segments decreased spontaneous activity and excitatory CRD responses of 33/56 cells and increased spontaneous activity of 13/19 cells inhibited by CRD. Glutamate applied to C6–C7 segments decreased activity of 10/18 cells excited by CRD, and 9 of these also were inhibited by glutamate at C1–C2 segments. Glutamate at C6–C7 increased activity of 4/6 cells inhibited by CRD and excited by glutamate at C1–C2 segments. After transection at rostral C1 segment, glutamate at C1–C2still reduced excitatory responses of 7/10 cells. Further, inhibitory effects of C6–C7 glutamate on excitatory responses to CRD still occurred after rostral C1transection but were abolished after a rostral C6transection in 4/4 cells. These data showed that C1–C2 cells activated with glutamate primarily produced inhibition of evoked responses to visceral stimulation of lumbosacral spinal cells. Inhibition resulting from activation of cells in C6–C7 segments required connections in the upper cervical segments. These results provide evidence that upper cervical cells integrate information that modulates activity of distant spinal neurons responding to visceral input.

1999 ◽  
Vol 82 (5) ◽  
pp. 2092-2107 ◽  
Author(s):  
Harumitsu Hirata ◽  
James W. Hu ◽  
David A. Bereiter

Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO2 pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO2 stimulation. The evoked activity of most cells occurred at 60% CO2 after a delay of 7–22 s. At the Vi/Vc transition three response patterns were seen. Type I cells ( n = 11) displayed an increase in activity with increasing CO2 concentration. Type II cells ( n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO2 concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO2 pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO2-responsive cells ( n = 15) displayed an increase in firing rates with greater CO2 concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO2 pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5–3.5 mg/kg iv) enhanced the CO2-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO2 stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways.


1993 ◽  
Vol 70 (5) ◽  
pp. 1950-1961 ◽  
Author(s):  
A. R. Evans ◽  
R. W. Blair

1. Various intensities, frequencies, and pulse widths of electrical stimulation of vagal afferent fibers were used to assess the responses of 87 medullary raphe neurons to vagal afferent fiber input in pentobarbital sodium-anesthetized, barodenervated paralyzed cats. Thirty-seven neurons were antidromically activated from the T2-T3 segments of the thoracic spinal cord, and 40 neurons could not be antidromically activated. Neurons were located in the nucleus raphe magnus (79%) and the nucleus raphe obscurus (15%). The remaining 6% of the neurons were not found; however, their locations were comparable in depth and position on the midline with other neurons in the same animals whose locations were identified. 2. The responses of 60 neurons to electrical stimulation of vagal afferent fibers were classified as excitatory (38%), inhibitory (24%), or mixed, (7%). The mixed responses were characterized by excitation at one frequency or intensity and inhibition at another frequency or intensity. The remaining 27 neurons did not clearly respond. 3. The excitatory responses to electrical stimulation of the cervical vagus nerve were intensity and frequency dependent. Inhibitory responses were frequency dependent at lower frequencies of stimulation and both frequency and intensity dependent at higher frequencies. The mixed responses were frequency dependent. Overall, longer pulse widths produced significantly greater responses than shorter pulse widths. 4. Thirty-three neurons were tested for responses to chemical stimulation of vagal afferents with intra-atrial injections of three doses of veratridine. Twenty-one percent were excited, 55% were inhibited, and 6% had mixed responses. For the mixed responses, excitation occurred at one dose and inhibition at another. The remaining 18% of the neurons were unresponsive to veratridine. The excitatory responses were dose dependent, but the inhibitory responses were not. Three doses of phenybiguanide (PBG) were also used to chemically activate vagal afferents in 27 neurons. Eleven percent were excited, 44% were inhibited, and 4% had mixed responses. The remaining 41% were unresponsive to PBG. The excitatory and inhibitory responses were dose dependent. 5. When comparing responses in projection and nonprojection neurons, inhibition was seen significantly more often in projection neurons and excitation in nonprojection neurons. Sixty-three percent of the neurons inhibited by electrical stimulation were raphespinal neurons, and 78% of the neurons excited by vagal stimulation were nonprojection neurons. Similar observations were made with the responses to chemical activation of the vagus. 6. Neurons with lower spontaneous discharge rates were more often excited by vagal stimulation and neurons with higher rates were more often inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)


Author(s):  
Zhenjun T TAN ◽  
Matthew Ward ◽  
Robert J Phillips ◽  
Xueguo Zhang ◽  
Deborah M Jaffey ◽  
...  

Gastric electrical stimulation (GES) is used clinically to promote proximal GI emptying and motility. In acute experiments, we measured duodenal motor responses elicited by GES applied at 141 randomly chosen electrode sites on the stomach serosal surface. Overnight-fasted (H2O available) anesthetized male rats (n = 81) received intermittent biphasic GES for 5 min (20s-on/40s-off cycles; I = 0.3mA; pw = 0.2ms; 10 Hz). A strain gauge on the serosal surface of the proximal duodenum of each animal was used to evaluate baseline motor activity and the effect of GES. Using ratios of time blocks compared to a 15-min pre-stimulation baseline, we evaluated the effects of the 5-min stimulation on concurrent activity; on the 10-min immediately after the stimulation, and on the 15-min period beginning with the onset of stimulation. We mapped the magnitude of the duodenal response (3 different motility indices) elicited from the 141 stomach sites. Post hoc electrode site maps associated with duodenal responses suggested three zones similar to the classic regions of forestomach, corpus and antrum. Maximal excitatory duodenal motor responses were elicited from forestomach sites, whereas inhibitory responses occurred with stimulation of the corpus. Moderate excitatory duodenal responses occurred with stimulation of the antrum. Complex, weak inhibitory/excitatory responses were produced by stimulation at boundaries between stomach regions. Patterns of GES efficacies coincided with distributions of previously mapped vagal afferents, suggesting that excitation of the duodenum is strongest when GES electrodes are situated over stomach concentrations of vagal intramuscular arrays, putative stretch receptors in the muscle wall.


2004 ◽  
Vol 286 (6) ◽  
pp. R1069-R1076 ◽  
Author(s):  
Fang Lu ◽  
Chao Qin ◽  
Robert D. Foreman ◽  
Jay P. Farber

Chemical activation of upper cervical spinal neurons modulates activity of thoracic respiratory interneurons in rats. The aim of the present study was to examine the effects of chemical activation of C1-C2 spinal neurons on thoracic spinal respiratory motor outflows. Electroneurograms of left phrenic ( n = 23) and intercostal nerves (ICNs, n = 93) between T3 and T8 spinal segments were recorded from 36 decerebrated, vagotomized, paralyzed, and ventilated male rats. To activate upper cervical spinal neurons, glutamate pledgets (1 M, 1 min) were placed on the dorsal surface of the C1-C2 spinal cord. Glutamate on C1-C2 increased ICN tonic activity in 56/59 (95%) ICNs. The average maximal tonic activity of ICN was increased by 174% ( n = 59). After spinal transection at rostral C1, glutamate on C1-C2 still increased ICN tonic activity in 33/35 ICNs. However, the effects of C1-C2 glutamate on ICN phasic activity were highly variable, with observations of augmentation or suppression of both inspiratory and expiratory discharge. C1-C2 glutamate augmented the average amplitude of phrenic burst by 20%, whereas the increases in amplitude of ICN inspiratory activity, when they occurred, averaged 120%. The burst rate of phrenic nerve discharge was decreased from 34.2 ± 1.6 to 26.3 ± 2.0 (mean ± SE) breaths/min during C1-C2 glutamate. These data suggested that upper cervical propriospinal neurons might play a role in descending modulation of thoracic respiratory and nonrespiratory motor activity.


2004 ◽  
Vol 91 (5) ◽  
pp. 2227-2235 ◽  
Author(s):  
Chao Qin ◽  
Margaret J. Chandler ◽  
Chuanchau J. Jou ◽  
Robert D. Foreman

Because vagal and sympathetic inputs activate upper cervical spinal neurons, we hypothesized that stimulation of the esophagus would activate C1–C2 neurons. This study examined responses of C1–C2 spinal neurons to cervical and thoracic esophageal distension (CED, TED) and afferent pathways for CED and TED inputs to C1–C2 spinal neurons. Extracellular potentials of single C1–C2 spinal neurons were recorded in pentobarbital-anesthetized male rats. Graded CED or TED was produced by water inflation (0.1–0.5 ml) of a latex balloon. CED changed activity of 48/219 (22%) neurons; 34 were excited (E), 12 were inhibited (I), and 2 were E-I. CED elicited responses for 18/18 neurons tested after ipsilateral cervical vagotomy, for 12/14 neurons tested after bilateral vagotomy and for 9/11 neurons tested after bilateral vagotomy and C6–C7 spinal cord transection. TED changed activity of 31/190 (16%) neurons (28E, 3 I). Ipsilateral cervical vagotomy abolished TED-evoked responses of 5/12 neurons. Bilateral vagotomy eliminated responses of 2/4 neurons tested, and C6–C7 spinal transection plus bilateral vagotomy eliminated responses of 2/2 neurons. Thus inputs from CED to C1–C2 neurons most likely entered upper cervical dorsal roots, whereas inputs from TED were dependent on vagal pathways and/or sympathetic afferent pathways that entered the thoracic dorsal roots. These results supported a concept that C1–C2 spinal neurons play a role in integrating visceral information from cervical and thoracic esophagus.


1962 ◽  
Vol 39 (3) ◽  
pp. 423-430
Author(s):  
H. L. Krüskemper ◽  
F. J. Kessler ◽  
E. Steinkrüger

ABSTRACT 1. Reserpine does not inhibit the tissue respiration of liver in normal male rats (in vitro). 2. The decrease of tissue respiration of the liver with simultaneous morphological stimulation of the thyroid gland after long administration of reserpine is due to a minute inhibition of the hormone synthesis in the thyroid gland. 3. The morphological alterations of the thyroid in experimental hypothyroidism due to perchlorate can not be prevented with reserpine.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan A. Shulgach ◽  
Dylan W. Beam ◽  
Ameya C. Nanivadekar ◽  
Derek M. Miller ◽  
Stephanie Fulton ◽  
...  

AbstractDysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.


1966 ◽  
Vol 51 (2) ◽  
pp. 281-289 ◽  
Author(s):  
J. Moll ◽  
G. H. Zeilmaker

ABSTRACT Castrated young adult inbred male rats bearing ovarian transplants were subjected to electrical stimulation of the hypothalamus. This was done in order to investigate whether discharge of ovulatory amounts of gonadotrophins could be induced in such male animals by this procedure. Bilateral stimulations with unipolar electrodes and a DC current of 1.5 mA applied during 10 seconds induced in the ovarian grafts histological changes indicating the discharge of ovulatory amounts of gonadotrophins. In animals killed one day after stimulation these changes consisted of displacement of the ova towards the centre of the follicles with loosening of the cumulus oophorus. In one animal the ova had left the follicles. In animals killed three days after stimulation numerous young corpora lutea could be observed. These results were obtained with electrode tips either close to the median eminence, or in the preoptic area. Shamstimulations were ineffective. Some of the experimental animals received progesterone pretreatment. This rendered the stimulations ineffective, if continued until the day preceding stimulation, but seemed without effect on the results of stimulation, if two or three days without progesterone preceded the stimulations.


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