Kainic acid on the rostral ventrolateral medulla inhibits phrenic output and CO2 sensitivity

1988 ◽  
Vol 65 (4) ◽  
pp. 1525-1534 ◽  
Author(s):  
E. E. Nattie ◽  
J. W. Mills ◽  
L. C. Ou ◽  
W. M. St John
Keyword(s):  
Kainic Acid ◽  
Neuronal Cell ◽  
Ventral Surface ◽  
Ventrolateral Medulla ◽  
Co2 Response ◽  
Specific Amino Acid ◽  
Amino Acid Receptors ◽  
Neuronal Cell Bodies ◽  
Chemosensitive Areas ◽  
End Tidal

We used the neurotoxin, kainic acid, which is known to stimulate neuronal cell bodies as opposed to axons of passage by binding to specific amino acid receptors to determine whether cells with such receptors have access to the ventrolateral medullary surface and are involved in central ventilatory chemosensitivity. Pledgets with 4.7 mM kainic acid were placed bilaterally on the rostral, intermediate, or caudal ventilatory chemosensitive areas for 1-2 min in chloralose-urethan-anesthetized, paralyzed, vagotomized, glomectomized, and servo-ventilated cats. Application of kainic acid on the caudal or intermediate areas produced no consistent significant effects on eucapnic phrenic output or on the slope or maximum value of the phrenic nerve response to increased end-tidal PCO2. Rostral area kainic acid produced immediate augmentation and then diminution of blood pressure and phrenic output. Apnea developed in six of nine cats by 40 min. In all five cats in which it could be tested, the slope of the CO2 response was clearly decreased. Of [3H]kainic acid applied to the rostral area, 88.4% was shown to be within 2 mm of the ventral surface. Comparison of surface application sites of this and other studies suggests that an area overlapping the border of the original rostral and intermediate areas allows access to neurons involved in the chemoreception process, which may also provide tonic facilitatory input to cardiorespiratory systems.

Excitatory amino acid receptors in commissural nucleus of the NTS mediate carotid chemoreceptor responses

1993 ◽  
Vol 264 (1) ◽  
pp. R41-R50 ◽  
Author(s):  
A. Vardhan ◽  
A. Kachroo ◽  
H. N. Sapru
Keyword(s):  
Amino Acid ◽  
Carotid Body ◽  
Excitatory Amino Acid ◽  
Minute Ventilation ◽  
Neuronal Cell ◽  
Excitatory Amino Acid Receptors ◽  
Amino Acid Receptors ◽  
Neuronal Cell Bodies ◽  
Carotid Body Chemoreceptors ◽  
Stimulation Of

Stimulation of carotid body chemoreceptors by saline saturated with 100% CO2 elicited an increase in mean arterial pressure, respiratory rate, tidal volume, and minute ventilation (VE). Microinjections of L-glutamate into a midline area 0.5-0.75 mm caudal and 0.3-0.5 mm deep with respect to the calamus scriptorius increased VE. Histological examination showed that the site was located in the commissural nucleus of the nucleus tractus solitarii (NTS). The presence of excitatory amino acid receptors [N-methyl-D-aspartic acid (NMDA); kainate, quisqualate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and trans 1-amino-cyclopentane-trans-1,3-dicarboxylic acid (ACPD)] in this area was demonstrated by microinjections of appropriate agonists. Simultaneous blockade of NMDA and non-NMDA receptors by combined injections of DL-2-aminophosphonoheptanoate (AP-7; 1 nmol) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 1 nmol) abolished the responses to stimulation of carotid body on either side. Combined injections of AP-7 and DNQX did not produce a nonspecific depression of neurons because the responses to another agonist, carbachol, remained unaltered. Inhibition of the neurons in the aforementioned area with microinjections of muscimol (which hyperpolarizes neuronal cell bodies but not fibers of passage) also abolished the responses to subsequent carotid body stimulation on either side.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory effects of kainic acid injection of the ventrolateral solitary nucleus

1982 ◽  
Vol 52 (1) ◽  
pp. 131-140 ◽  
Author(s):  
A. J. Berger ◽  
K. A. Cooney
Keyword(s):  
Kainic Acid ◽  
Minute Ventilation ◽  
Neuronal Cell ◽  
Neuronal Loss ◽  
Long Term Effects ◽  
Awake State ◽  
Ventilatory Responses ◽  
Neuronal Cell Bodies ◽  
Ventilatory Effects ◽  
Kainic Acid Injection

We studied in cats the long-term effects upon resting ventilation and the ventilatory responses to CO2 breathing of destruction of neuronal cell bodies within the ventrolateral nucleus of the tractus solitarius (vl-NTS) by kainic acid (KA) injection (KAI). Animals were studied in the awake state and under pentobarbital anesthesia both before and 8 wk after stereotaxic bilateral microinjection of the vl-NTS with mock cerebrospinal fluid (CSF) (controls, n = 2) or with KA in mock CSF (KAI, n = 5). KA reduced the number of cell bodies within the vl-NTS by 75%. Under anesthesia minute ventilation (VI) was reduced by 49% after KAI, due primarily to a 54% reduction in breathing frequency (f). Four of five anesthetized KAI animals exhibited a significantly reduced (P less than 0.01) ventilatory sensitivity to inspired CO2 under anesthesia. In the awake state some KAI animals had significant changes (P less than 0.01) in ventilation; VI reduced (2 of 5), tidal volume reduced (1 of 5), f reduced (3 of 5), and inspiratory and expiratory times increased (2 of 5). Decreases in the awake ventilatory CO2 sensitivity were not significant within individual KAI animals but were significant (P less than 0.05) when considered as a group. Thus following 75% neuronal loss within the vl-NTS, rhythmic ventilation was sustained during both anesthesia and wakefulness, although f was reduced in the former state. The vl-NTS may function to set most but not all of the ventilatory sensitivity to CO2 during anesthesia and to a lesser extent during wakefulness.

Nucleus Gracilis: An Integrator for Visceral and Somatic Information

1997 ◽  
Vol 78 (1) ◽  
pp. 521-527 ◽  
Author(s):  
Elie D. Al-Chaer ◽  
Karin N. Westlund ◽  
William D. Willis
Keyword(s):  
Kainic Acid ◽  
Visceral Pain ◽  
Neuronal Cell ◽  
Dorsal Column ◽  
Sprague Dawley ◽  
Nucleus Gracilis ◽  
Abdominal Organs ◽  
Neuronal Cell Bodies ◽  
Sprague Dawley Rats ◽  
Before And After

Al-Chaer, Elie D., Karin N. Westlund, and William D. Willis. Nucleus gracilis: an integrator for visceral and somatic information. J. Neurophysiol. 78: 521–527, 1997. The nucleus gracilis (NG) receives an abundance of visceral input from various abdominal organs and is proposed to play an important role in visceral pain processing. The purpose of this study was to investigate the necessity of the NG for colorectal input into the ventral posterolateral (VPL) nucleus of the thalamus. Single-cell recordings were made from nine VPL cells isolated in nine different male Sprague Dawley rats anesthetized with pentobarbital sodium. Responses of the VPL cells to colorectal distension (CRD) and to cutaneous stimuli were obtained before and after lesioning of the NG. Electrolytic ( n = 5) and chemical ( n = 4) lesions of the NG were made in different preparations. The chemical lesions were made by injecting a solution of kainic acid into the NG. Kainic acid presumably kills neuronal cell bodies and spares axons of passage. The results indicate that a lesion of the NG, regardless of its type, reduces dramatically the responses of VPL neurons to innocuous cutaneous stimuli, and, to a lesser extent, the responses to CRD. Attenuation of VPL neuronal responses to CRD as well as to innocuous cutaneous stimuli by the NG lesions emphasizes the role of the dorsal column in visceral nociception and suggests that the NG is an integration center for visceral and cutaneous information flowing into the VPL nucleus.

Pirenzepine prevents diethyl pyrocarbonate inhibition of central CO2 sensitivity

1988 ◽  
Vol 65 (5) ◽  
pp. 1962-1966 ◽  
Author(s):  
E. E. Nattie ◽  
J. W. Mills ◽  
L. C. Ou
Keyword(s):  
Ventral Surface ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Inhibitory Effects ◽  
Co2 Sensitivity ◽  
Diethyl Pyrocarbonate ◽  
Maximum Value ◽  
Chemosensitive Areas ◽  
Co2 Chemosensitivity

Application by pledget of the M1-antimuscarinic receptor agent pirenzepine (40 mM) to the rostral chemosensitive areas of the ventrolateral medulla in anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated cats inhibited the slope of the integrated phrenic response to CO2 by 32.5% (P less than 0.03) and the maximum value by 21.1% (P less than 0.01). Similar application of the imidazole-histidine blocking agent diethyl pyrocarbonate (DEPC) decreased the slope by 40.3% (P less than 0.01) and the maximum value by 29.3% (P less than 0.05). Both responses confirm previous results. DEPC treatment decreased the effectiveness of subsequent pirenzepine application such that although slope and maximum were further decreased, the values were not significantly different from those after DEPC. Pirenzepine treatment prevented any subsequent DEPC inhibitory effect. The results raise the possibility that the inhibitory effects of DEPC on CO2 chemosensitivity are via muscarinic receptors and that muscarinic receptor involvement in CO2 chemosensitivity requires the presence of imidazole-histidine. Analysis by scintillation counting of successive 100-micron sections of medulla after rostral area application of [3H]pirenzepine indicated that the pirenzepine and DEPC effects are most probably within 2.0 mm of the ventral surface as measured from the midline, well away from the dorsal and ventral respiratory group neurons.

Central effects of endothelin on respiratory output during development

1995 ◽  
Vol 79 (2) ◽  
pp. 420-427 ◽  
Author(s):  
I. A. Dreshaj ◽  
M. J. Miller ◽  
P. Ernsberger ◽  
B. Haxhiu-Poskurica ◽  
R. J. Martin ◽  
...  
Keyword(s):  
Specific Binding ◽  
Respiratory Control ◽  
Ventral Surface ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Postnatal Life ◽  
Receptor Blockade ◽  
Endothelin 1 ◽  
Chemosensitive Areas ◽  
Endothelin A

Both endothelin-1 protein and endothelin-1 specific binding sites have been identified in areas of the medulla oblongata involved in respiratory control. We examined whether endothelin acting centrally affects respiratory output during early postnatal life. We initially examined the effect of intracisternally administrated endothelin on respiratory output in 10 2- to 18-day-old piglets. Endothelin-1 administration at 50 nmol to 1 mumol caused respiratory inhibition. We subsequently examined whether this response is mediated through chemosensitive areas of the ventral medulla. Endothelin-1 was microinjected into specific ventral or dorsal medullary regions in 31 14- to 22-day-old piglets. Microinjection of endothelin-1 (10 fmol to 0.1 pmol) just above the hypoglossal roots, lateral to the pyramids, and within 1 mm from the surface (n = 24) attenuated respiratory output, and complete apnea occurred with 1 pmol in all animals. However, microinjection of endothelin-1 3 mm below the ventral surface (n = 5) and into the dorsal medulla (n = 3) had no inhibitory effect. Comparable doses of angiotensin II (n = 5) and norepinephrine (n = 5) microinjected into the endothelin-1 sensitive area also did not influence respiratory output. These effects of endothelin-1 were not altered by prior endothelin-B receptor blockade (IRL-1038) but could be reversed by endothelin-A receptor blockade (BQ-610). These results suggest that endothelin-1 release may cause ventilatory depression mediated through endothelin-A receptors located in the chemosensitive areas of the ventrolateral medulla.

Cardiac sympathetic premotor neurons

1997 ◽  
Vol 272 (2) ◽  
pp. R615-R620 ◽  
Author(s):  
R. R. Campos ◽  
R. M. McAllen
Keyword(s):  
Injection Site ◽  
Neuronal Cell ◽  
Sympathetic Nerves ◽  
Ventrolateral Medulla ◽  
Response Ratio ◽  
Cardiac Nerve ◽  
Neuronal Cell Bodies ◽  
Premotor Neurons ◽  
Sympathetic Premotor Neurons ◽  
Inferior Cardiac Nerve

To locate premotor neurons controlling the cardiac sympathetic supply and to determine their relation to brain stem vasomotor pathways, the rostral ventrolateral medulla (RVLM) was mapped in seven chloralose-anesthetized cats, with the use of microinjections of sodium glutamate (5-10 nl, 0.1 M) to excite neuronal cell bodies. Cardiac sympathetic responses were recorded from the ipsilateral inferior cardiac nerve, while recordings were made simultaneously from postganglionic vasoconstrictor fibers to skeletal muscle (ipsilateral peroneal nerve). Baroreceptors were denervated to eliminate the reflex effects of blood pressure changes. Most of the 115 injected RVLM sites excited both sympathetic nerves. Inferior cardiac nerve activity increased by up to 395% (mean 105 +/- 86%, SD), and muscle vasoconstrictor activity increased by up to 487% (110 +/- 107%). Their relative response varied with injection site, however. For 16 of the most rostromedial injections, the inferior cardiac nerve-to-muscle vasoconstrictor response ratio exceeded that expected by two- to sevenfold; for 9 very caudolateral injections that ratio was strongly reversed, favoring muscle vasoconstrictors by two to fivefold. Intervening sites gave more equal responses. Overall, the response ratio varied systematically with injection site. These findings demonstrate that neurons with preferential or selective actions on the cardiac sympathetic outflow are present in the RVLM and are organized topographically. The simplest interpretation is that a population of selective cardiac sympathetic premotor neurons occupies a territory substantially overlapping, but centered rostromedially to, the population controlling vasoconstriction in muscle.

Differentiation of two cardiovascular regions within caudal ventrolateral medulla

1991 ◽  
Vol 261 (4) ◽  
pp. R985-R994 ◽  
Author(s):  
S. L. Cravo ◽  
S. F. Morrison ◽  
D. J. Reis
Keyword(s):  
Arterial Pressure ◽  
Kainic Acid ◽  
Neuronal Activity ◽  
Pressor Response ◽  
Neuronal Cell ◽  
Baroreceptor Reflex ◽  
Ventrolateral Medulla ◽  
Reticular Nucleus ◽  
Lateral Reticular Nucleus ◽  
Caudal Ventrolateral Medulla

The caudal ventrolateral medulla (CVLM) plays a significant role in the regulation of sympathetic nerve activity (SNA) and arterial pressure; however, the use of lesions to examine its role in mediating baroreceptor reflex control of SNA has yielded discrepant results. We hypothesize that this may have arisen from anatomic segregation of neurons within the CVLM that subserve different functions in sympathetic control. Thus we used microinjections of the excitotoxic agent kainic acid (200 pmol in 20 nl) to determine the effects of inactivation of neuronal cell bodies in a rostral and a caudal subregion of the CVLM on SNA, arterial pressure, and baroreceptor reflex function in urethan-anesthetized rats. Interruption of neuronal activity in the rostral CVLM (sites from 0.6 mm caudal to 0.5 mm rostral to the rostral border of the lateral reticular nucleus) elevated SNA (post-kainic acid 214% of control) and arterial pressure (+34 mmHg) and eliminated the inhibition of splanchnic SNA evoked by either aortic nerve stimulation or the pressor response to intravenous norepinephrine. In addition, the cardiac-related component of spontaneous SNA was abolished as judged from post-R wave averages and from power spectral analysis. In contrast, although a similar disruption of neuronal activity in the caudal CVLM (sites 0.0-0.6 mm rostral to the caudal border of the lateral reticular nucleus) produced a comparable increase in spontaneous SNA (post-kainic acid 196% of control) and arterial pressure (+20 mmHg), it was without effect on the ability of the baroreceptor reflex to inhibit SNA, and it enhanced the synchronization of the spontaneous bursts in SNA to the cardiac cycle. Our results suggest an organization of the CVLM in which neurons in its rostral portion are required for an effective baroreceptor reflex, whereas those in the caudal CVLM serve to limit SNA and blood pressure independent of the baroreceptor reflex.

Diethyl pyrocarbonate (an imidazole binding substance) inhibits rostral VLM CO2 sensitivity

1986 ◽  
Vol 61 (3) ◽  
pp. 843-850 ◽  
Author(s):  
E. E. Nattie
Keyword(s):  
Ventrolateral Medulla ◽  
Initial Slope ◽  
Rank Test ◽  
Co2 Response ◽  
Central Chemosensitivity ◽  
Diethyl Pyrocarbonate ◽  
Before And After ◽  
Wilcoxon Sign Rank ◽  
Chemosensitive Areas

Diethyl pyrocarbonate (DEPC) has been useful in vitro as an agent relatively specific for binding to imidazole of histidine. Administered via the cisterna magna DEPC inhibits central chemosensitivity in conscious rabbits, supporting the alphastat hypothesis for central chemoreceptor function. In this study I have applied DEPC via 1 X 3 mm cottonoid pledgets to each of the three ventrolateral medulla (VLM) chemosensitive areas in glomectomized, vagotomized, paralyzed, and servo-ventilated alpha-chloralose-urethan-anesthetized cats. CO2 responses measured by integrated phrenic nerve output were evaluated before and after DEPC application. A dose of 40 mmol/l applied to the rostral chemosensitive area increased the CO2 threshold (5.3%) and significantly decreased (P less than 0.03; Wilcoxon sign rank test) the initial slope (-43%) and the maximum (-41%) of the CO2 response. No significant effects were observed with DEPC application in the intermediate or caudal areas. Treatment with 40 mmol/l hydroxylamine immediately after DEPC in the rostral area prevented the effects supporting the interpretation that imidazole was the reactant with DEPC. The results are consistent with the hypothesis that imidazole-histidine is involved in the mechanism of central chemoreception and indicate that only the rostral area utilizes a DEPC inhibitable mechanism.

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