Fastigial nucleus-mediated respiratory responses depend on the medullary gigantocellular nucleus.

Electrical stimulation of the rostral fastigial nucleus (FNr) alters respiration via activation of local neurons. We hypothesized that this FNr-mediated respiratory response was dependent on the integrity of the nucleus gigantocellularis of the medulla (NGC). Electrical stimulation of the FNr in 15 anesthetized and tracheotomized spontaneously breathing rats significantly altered ventilation by 35.2 +/- 11.0% (P < 0.01) with the major effect being excitatory (78%). This respiratory response did not significantly differ from control after lesions of the NGC via bilateral microinjection of kainic or ibotenic acid (4.5 +/- 1.9%; P > 0.05) but persisted in sham controls. Eight other rats, in which horseradish peroxidase (HRP) solution was previously microinjected into the left NGC, served as nonstimulation controls or were exposed to either 15-min repeated electrical stimulation of the right FNr or hypercapnia for 90 min. Histochemical and immunocytochemical data showed that the right FNr contained clustered HRP-labeled neurons, most of which were double labeled with c-Fos immunoreactivity in both electrically and CO(2)-stimulated rats. We conclude that the NGC receives monosynaptic FNr inputs and is required for fully expressing FNr-mediated respiratory responses.     

Kainic acid lesions of the median preoptic nucleus: effects on angiotensin II induced drinking and pressor responses in the conscious rat

Input to the nucleus medianus of the preoptic region has been suggested to be involved in both the drinking and pressor responses elicited by the central administration of angiotensin II. Evidence in support of this suggestion has been gained principally from electrical lesion experiments. This lesion procedure does not differentiate between the cells of the region and fibers coursing through the region. To test the hypothesis that cells in this region are involved in both the pressor and drinking responses elicited by central administration of angiotensin II, injections of kainic acid were made to induce lesions of the cells, while sparing fibers of passage. Drinking and blood pressure responses were determined pre- and post-lesion in the chronically instrumented awake rat. Injections of 50 ng angiotensin II in a 2-microL volume into a lateral cerebral ventricle of the conscious rat elicited pronounced drinking and pressor responses with a latency of 3-5 min. Lesions of the median preoptic region produced by injecting 1.0 microgram of kainic acid in 0.25 microL for 15 s attenuated or blocked the drinking response and increased the latency to drink induced by central injections of angiotensin II. However, kainic acid lesions did not significantly alter the pressor responses produced by angiotensin II administration. These results suggest that cells in the median preoptic region are involved in the drinking response but do not participate in the pressor response elicited by angiotensin II administration into a lateral cerebral ventricle of the conscious rat.     

Effect of paraventricular nucleus lesions on cardiovascular responses elicited by stimulation of the subfornical organ in the rat

It has recently been reported that stimulation of the region of the subfornical organ (SFO) elicits an increase in arterial pressure. However, the mechanisms and forebrain neural circuitry that are involved in this cardiovascular response have not been elucidated. The present study was done in urethane-anaesthetized rats to determine whether selective activation of SFO neurons elicit cardiovascular responses and whether these responses were mediated by a pathway involving the paraventricular nucleus of the hypothalamus (PVH). Stimulation sites which required the lowest threshold current (30 microA) to elicit a pressor response and at which the largest rise in mean arterial pressure (MAP; 22 +/- 2 mmHg) was elicited at a constant current intensity (150 microA) were histologically localized in the region of the SFO. Short (mean peak latency; 4 +/- 2 s) and long (mean peak latency; 61 +/- 8 s) latency increases in MAP were observed during and after electrical stimulation of the SFO, respectively. Cardiac slowing accompanied the short latency pressor response and cardioacceleration was observed in most (57%) of the cases to accompany the late pressor response. Microinjection of L-glutamate into the SFO consistently elicited cardiovascular responses qualitatively similar to those observed during electrical stimulation. Ganglionic blockade abolished the short latency increase in MAP and the accompanying bradycardia. However, the long latency pressor and cardioacceleratory responses were not altered by ganglionic blockade and adrenalectomy. Selective bilateral electrolytic or kainic acid lesions of the region of the PVH significantly attenuated the cardiovascular responses elicited by stimulation of the SFO. These data suggest that activation of neurons in the SFO elicit cardiovascular responses partially mediated by sympathetic outflow through a neural pathway involving the PVH.     

Parabrachial neurons mediate dorsal periaqueductal gray evoked respiratory responses in the rat.

The neural substrates mediating autonomic components of the behavioral defense response reside in the periaqueductal gray (PAG). The cardiovascular components of the defense response evoked from the dorsal PAG (DPAG) have been well described and are dependent, in part, on the integrity of neurons in the region of the parabrachial nucleus as well as the rostral ventrolateral medulla. Descending pathways mediating the ventilatory response associated with activation of DPAG neurons are unknown. The present study was undertaken to test the hypothesis that parabrachial area neurons are also involved in mediating the respiratory response to DPAG stimulation. In urethane-anesthetized, spontaneously breathing rats, electrical stimulation of the DPAG significantly increased respiratory rate, arterial pressure, and heart rate. Changes in respiratory frequency were associated with significant decreases in inspiratory and expiratory durations. After bilateral inhibition of neurons in the lateral parabrachial nucleus (LPBN) region with 5 mM muscimol (n = 6), DPAG-evoked increases in respiration and heart rate were attenuated by 90 +/- 6 and 72 +/- 13%, respectively. The pressor response evoked by DPAG stimulation, however, was attenuated by only 57 +/- 6%. Bilateral blockade of glutamate receptors with 20 mM kynurenic acid (n = 6) in the LPBN also markedly attenuated DPAG-evoked increases in respiration and heart rate (65 +/- 15 and 53 +/- 9% reduction, respectively) but only modestly changed the DPAG-evoked pressor response (34 +/- 16% reduction). These results demonstrate that LPBN neurons play a significant role in the DPAG-mediated respiratory component of behavioral defense responses. This finding supports previous work demonstrating that the dorsolateral pons plays a significant role in mediating most physiological adjustments associated with activation of the DPAG.     

Mechanisms underlying the cardioinhibitory and pressor responses elicited from the medullary neurons in the gigantocellular tegmental field of cats

A stimulation of the gigantocellular tegmental field (FTG) in the medulla oblongata often increases systemic arterial blood pressure (SAP) and decreases heart rate (HR). We investigated if the cardioinhibitory/depressor areas, including the nucleus ambiguus (NA), the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), underlied the functional expression of FTG neurons in regulating cardiovascular responses. In 73 chloralose-urethane anesthetized cats, the HR, SAP and vertebral nerve activity (VNA) were recorded. Neurons in the FTG, NA, DMV and CVLM were stimulated by microinjection of sodium glutamate (25 mM Glu, 70 nl). To study if the NA, DMV, and CVLM relayed the cardioinhibitory messages from the FTG, 24 mM kainic acid (KA, 100 nl) was used as an excitotoxic agent to lesion neurons in the NA, DMV or CVLM. We found that the cardioinhibition induced by FTG stimulation was significantly reduced by KA lesioning of the ipsilateral NA or DMV. Subsequently, a bilateral KA lesion of NA or DMV abolished the cardioinhibitory responses of FTG. Compared to the consequence of KA lesion of the DMV, only a smaller bradycardia was induced by FTG stimulation after KA lesion of the NA. The pressor response induced by Glu stimulation of the FTG was reduced by the KA lesion of the CVLM. Such an effect was dominant ipsilaterally. Our findings suggested that both NA and DMV mediated the cardioinhibitory responses of FTG. The pressor message from the FTG neurons might be partly working via a disinhibitory mechanism through the depressor neurons located in the CVLM.     

Medial vestibular nucleus mediates the cardiorespiratory responses to fastigial nuclear activation and hypercapnia.

Electrical stimulation of the cerebellar fastigial nucleus (FN) evokes hyperventilation and hypertension responses that are similar to those induced by stimulation of the medial region of the vestibular nucleus (VNM). Because there are mutual projections between these two nuclei morphologically, we hypothesized that the FN-mediated cardiorespiratory responses were related to the integrity of the VNM. Experiments were conducted on 21 anesthetized, tracheotomized, and spontaneously breathing rats. Electrical stimulation (approximately 10 s) of the FN was used to evoke cardiorespiratory responses, and the same stimulus was repeated 30-45 min after bilateral lesions of the VNM by local microinjection of ibotenic acid (100 mM, 100 nl). We found that FN stimulation-induced hyperventilation and hypertension were attenuated significantly by the lesions. The role of the VNM in the ventilatory responses to chemical challenges was subsequently defined. The animals were exposed to hypercapnia (10% CO2) and hypoxia (10% O2) for 1-2 min randomly before and after VNM lesions. The results showed that VNM lesions significantly attenuated the cardiorespiratory responses to hypercapnia but not to hypoxia, with little effect on baseline respiratory variables. These findings suggest that the VNM is required for full expression of the cardiorespiratory responses to electrical stimulation of the FN as well as to hypercapnia. However, neurons within the VNM do not appear to be critical for maintaining eupneic breathing and the cardiorespiratory responses to hypoxia.     

Retrofacial lesions: effects on CO2-sensitive phrenic and sympathetic nerve activity.

We made unilateral chemical (10- or 50-nl microinjections; 4.7 mM kainic acid) or electrolytic (5-15 mA; 15 s) lesions in a region of the rostral ventrolateral medulla (VLM) caudal to the retrotrapezoid nucleus in 10 decerebrate, paralyzed, vagotomized, and servo-ventilated cats. The lesions were 3.0-4.2 mm lateral to the midline, within 2 mm caudal to the facial nucleus, and within 2.5 mm of the VLM surface. Four control injections (mock cerebrospinal fluid and fluorescent beads alone) produced small and inconsistent effects over 3-5 h. The predominant effect of the lesions was a significant decrease in baseline integrated phrenic nerve amplitude (PNA) (apnea in 2 cases), total respiratory cycle duration, and the response to increased CO2 (slope < 15% of control in 3 cases). The respiratory-related peak amplitude of the integrated sympathetic signal, blood pressure, and the sympathetic nerve activity response to CO2 were also decreased after the majority of lesions. Not all lesions produced all effects, and some lesions resulted in increased PNA and respiratory cycle duration. The lesioned region appears functionally to represent a caudal extension of the retrotrapezoid nucleus containing neurons necessary for normal baseline PNA and CO2 sensitivity. In addition, it contains neurons involved in the determination of resting respiratory frequency and normal sympathetic activity and blood pressure. The pattern of mixed responses among animals suggests that a heterogeneity of function is present within a relatively small VLM region.     

Enhanced pressor response to carotid occlusion in commNTS-lesioned rats: possible efferent mechanisms

Bilateral common carotid occlusion (BCO) over a period of 60 s in conscious rats produces a biphasic pressor response, consisting of an early (peak) and late (plateau) phase. In this study we investigated 1) the effects of lesions of the commissural nucleus of the solitary tract (commNTS) on the cardiovascular responses produced by BCO in conscious rats and 2) the autonomic and humoral mechanisms activated to produce the pressor response to BCO in sham- and commNTS-lesioned rats. Both the peak and plateau of the pressor response produced by BCO increased in commNTS-lesioned rats despite the impairment of chemoreflex responses induced by intravenous potassium cyanide. In sham rats sympathetic blockade with intravenous prazosin and metoprolol, but not vasopressin receptor blockade with the Manning compound, reduced both components of BCO. In commNTS-lesioned rats the sympathetic blockade or vasopressin receptor blockade reduced both components of BCO. The results showed 1) the sympathetic nervous system, but not vasopressin, is important for the pressor response to BCO during 60 s in conscious sham rats; 2) in commNTS-lesioned rats, despite chemoreflex impairment, BCO produces an increased pressor response dependent on sympathetic activity associated with vasopressin release; and 3) the increment in the pressor response to BCO in commNTS-lesioned rats seems to depend only on vasopressin secretion.     

Subfornical organ-angiotensin II pressor system takes part in pressor response of emotional circuit

It has been proved that there are the subfornical organ (SFO)-nucleus paraventricularis (NPV)-rostral ventrolateral medulla (RVL) angiotension II (AngII) pressor system and the central amygdaloid nucleus (AC)-lateral hypothalamus/perifornical region (LH/PF) emotional pressor system in the brain. Because the LH/PF contains abundant AngII ergic neurons projecting to the SFO, the purpose of the present study was to examine whether the (SFO-NPV-RVL) AngII pressor system takes part in the AC-pressor response via AngII ergic neurons in the LH/PF. The results showed that (1) L-glutamate microinjection into the AC or LH/PF induced pressor responses. (2) Both the AC- and LH/PF-pressor responses could be reversed by preinjection of [Sar(1), Thr(8)]-angiotensin II (an antagonist of AngII) into either the SFO, NPV or RVL. Taken together with our previous findings that the projections of the CRF-ergic and SP-ergic neurons in the AC could activate the LH/PF, the above findings prove that: besides several known mechanisms of the brain AngII inducing pressor response, the (SFO-NPV-RVL) AngII pressor system also takes part in the AC-emotional pressor response via AngII ergic projections from the LH/PF to the SFO, which may be the neurophysiological basis of the brain AngII playing an important role in developing hypertension of the SHRs.     

Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2.

There is evidence that serotonin [5-hydroxytryptamine (5-HT)] is involved in the physiological responses to hypercapnia. Serotonergic neurons represent the major cell type (comprising 15-20% of the neurons) in raphe magnus nucleus (RMg), which is a medullary raphe nucleus. In the present study, we tested the hypothesis 1) that RMg plays a role in the ventilatory and thermal responses to hypercapnia, and 2) that RMg serotonergic neurons are involved in these responses. To this end, we microinjected 1) ibotenic acid to promote nonspecific lesioning of neurons in the RMg, or 2) anti-SERT-SAP (an immunotoxin that utilizes a monoclonal antibody to the third extracellular domain of the serotonin reuptake transporter) to specifically kill the serotonergic neurons in the RMg. Hypercapnia caused hyperventilation and hypothermia in all groups. RMg nonspecific lesions elicited a significant reduction of the ventilatory response to hypercapnia due to lower tidal volume (Vt) and respiratory frequency. Rats submitted to specific killing of RMg serotonergic neurons showed no consistent difference in ventilation during air breathing but had a decreased ventilatory response to CO(2) due to lower Vt. The hypercapnia-induced hypothermia was not affected by specific or nonspecific lesions of RMg serotonergic neurons. These data suggest that RMg serotonergic neurons do not participate in the tonic maintenance of ventilation during air breathing but contribute to the ventilatory response to CO(2). Ultimately, this nucleus may not be involved in the thermal responses to CO(2).     

The contribution of the principal and spinal trigeminal nuclei to the receptive field properties of thalamic VPM neurons in the rat

Primary sensory information from neurons innervating whisker follicles on one side of a rat's face is relayed primarily through two subnuclei of the brainstem trigeminal complex to the contralateral thalamus. The present experiments were undertaken to separate the contribution of the principal trigeminal nucleus (PrV) from that of the spinal trigeminal nucleus (SpV) to whisker evoked responses in the ventral posterior medial (VPM) nucleus in the adult rat thalamus. Extracellular single-unit responses of VPM neurons to controlled stimulation of the contralateral whiskers under urethane anesthesia were quantified in terms of receptive field size, modal latency, response probability and response magnitude. The SpV contribution to VPM cell responses was isolated by making kainic acid lesions of the PrV. The PrV contribution was ascertained by cutting the trigeminothalamic axons arising from SpV just before they cross the midline. After destruction of the PrV, the SpV pathway alone produced large receptive fields (mean: 9.04 whiskers) and long latency (mean: 11.07 ms) responses from VPM neurons. In contrast, PrV input alone (SpV disconnected) generated small receptive fields (mean: 1.06 whiskers) and shorter latency (mean: 6.74 ms) responses. With both pathways intact the average receptive field size was 2.4 whiskers and peak (modal) response latency was 7.33 ms. The responses with both pathways intact were significantly different from either pathway operating in isolation. Response probability and magnitude followed the same trend. We conclude that normal responses of individual VPM neurons represent the integration of input activity transmitted through both PrV and SpV pathways.     

脚内核在电针镇痛及兴奋尾壳核镇痛中的作用

用行为学和电生理学的方法 ,探讨脚内核在电针镇痛及兴奋尾壳核镇痛中的作用。脚内核微量注射红藻氨酸 7d后 ,电针对辐射热引起的大鼠缩腿潜伏期无明显影响 ,电针或兴奋尾壳核对丘脑束旁核神经元的伤害性反应亦无明显影响。与正常对照组电针或兴奋尾壳核产生的抑制作用相比有显著性差异 (P <0 .0 5 ) ;与脚内核微量注射生理盐水 7d后 ,电针可提高大鼠缩腿潜伏期 ,及电针或兴奋尾壳核对束旁核神经元伤害性反应的抑制作用相比 ,有显著性差异 (P <0 0 5 )。上述结果提示 ,脚内核在电针及兴奋尾壳核镇痛中发挥重要作用     

Phencyclidine-induced activation of ventral tegmental A10 dopamine neurons is differentially affected by lesions of the nucleus accumbens and medial prefrontal cortex

The nucleus accumbens and medial prefrontal cortex contain high concentrations of phencyclidine (PCP) binding sites as well as supply inhibitory and excitatory inputs to the ventral tegmental area (VTA). Thus these two regions could be instrumental in mediating the unique bimodal response of A10 neurons to systemically administered PCP. Therefore we evaluated electrophysiologically the effects of lesions of these two areas on this pattern of response. In sham-lesioned controls, i.v. injections of PCP elicited a typical dose-dependent bimodal effect which was characterized by an activation of A10 firing at low dose (reaching a maximum of +44% at 1 mg/kg) followed by a slowing of this response with larger doses. However, in animals with kainic acid or radiofrequency lesions of the nucleus accumbens, PCP produced only a unimodal response resulting in sustained and elevated (+88% in kainate and +55% in radiofrequency lesioned groups) firing rates. Notably, neither basal activity nor the degree of activation of the A10's at doses of PCP less than 1 mg/kg were affected by the lesions. In contrast, excitotoxic destruction of the medial prefrontal cortex had no effect on the response of A10 neurons to PCP even though basal activity was slightly elevated in this group. These results suggest that the inhibitory component of the bimodal response of VTA neurons to systemic PCP is mediated via feedback pathways from the nucleus accumbens, but that the mesocortical prefrontal cortex does not appear to modulate any portion of this bimodal response.     

ANG II in median preoptic nucleus and pressor responses to CSF sodium and high sodium intake in SHR

Pressor responses to increases in cerebrospinal fluid (CSF) sodium in Wistar rats and to high salt intake in spontaneously hypertensive rats (SHR) involve both brain ouabainlike activity ("ouabain") and the brain renin-angiotensin system (RAS). Because some of the effects of "ouabain" are mediated by the median preoptic nucleus (MnPO) and this nucleus contains all elements of the RAS, the present study assessed possible interactions of "ouabain" and ANG II in this nucleus. In conscious Wistar rats, injection of ANG II into the MnPO significantly increased mean arterial pressure (MAP) and heart rate (HR). This response was not affected by pretreatment with a subpressor dose of ouabain. MAP and HR increases by ouabain in the MnPO were significantly attenuated by MnPO pretreatment with losartan. In Wistar rats, losartan in the MnPO also abolished pressor and HR responses to intracerebroventricular 0.3 M NaCl and attenuated MAP and HR responses to intracerebroventricular ouabain. Five weeks of a high-salt diet in SHRs resulted in exacerbation of hypertension and increased responses to air-jet stress and intracerebroventricular guanabenz. Losartan injected into the MnPO reversed the salt-sensitive component of the hypertension and normalized the depressor response to guanabenz but did not change responses to air-jet stress. We conclude that in the MnPO, ANG II via AT(1) receptors mediates cardiovascular responses to an acute increase in CSF sodium as well as the chronic pressor responses to high sodium intake in SHR.     

Central control of cardiac baroreflex responses during peripheral hyperosmolality

Acute increases in peripheral osmolality evoke a pressor response and baroreflex-mediated bradycardia. These experiments were designed to determine if the fall in heart rate during peripheral sodium loading is 1) equivalent to bradycardia accompanying phenylephrine (PE) infusion, 2) mediated by the parasympathetic (PSNS) or sympathetic (SNS) nervous system, and 3) controlled by the median preoptic nucleus (MnPO). Male rats received an intravenous infusion of isotonic saline, hypertonic saline (2.5 M NaCl), or PE for 30 min. Blood pressure increased equivalently in the hypertonic NaCl and PE groups. However, heart rate fell more in animals infused with PE. Furthermore, pretreatment with methylatropine to block the PSNS had no effect on bradycardia, whereas blocking SNS influences on cardiac function significantly attenuated the fall in heart rate during peripheral hyperosmolality. Finally, kainic acid administration in the MnPO before testing increased bradycardia observed during hypertonic saline loading. Taken together, these data suggest that acute peripheral hyperosmolality acts at the MnPO to reduce cardiac SNS withdrawal during the pressor response that reduces the associated baroreflex bradycardia.     

Cough and laryngeal muscle discharges in brainstem lesioned anaesthetized cats

Experiments were carried out to determine whether there are separate drives from the selected neuronal networks of the brainstem affecting the discharge patterns of laryngeal and respiratory pump muscles during cough. Twenty-four non-decerebrate spontaneously breathing cats anesthetized with sodium pentobarbitone were used. Microinjections of kainic acid into the lateral tegmental field of the medulla, medullary midline or pontine respiratory group eliminated the cough evoked by mechanical stimulation of the tracheobronchial and laryngopharyngeal mucosa. These stimuli, in most cases, provoked irregular bursts of discharges in the posterior cricoarytenoid and thyroarytenoid laryngeal muscles (or they had no effect on them). No pattern of laryngeal muscle activities following lesions resembled the laryngeal cough response. Lesions of the target regions did not result in any apparent changes in the eupnoeic pattern of laryngeal activity. Neurons of the medullary lateral tegmental field, raphe nuclei and the pontine respiratory group seem to be indispensable for the configuration of the central cough motor pattern. However, these neurons do not appear to be essential for the discharge patterns of laryngeal motoneurons during eupnoea. The residual laryngeal "cough" responses are probably mediated by an additional motor drive.     

脑内P物质在谷氨酸兴奋腹内侧核引起的升压反应中之作用

目的：分析谷氨酸兴奋下兵脑腹内侧核（NVM）引起升压反应的机制。方法：大鼠脑内或静脉注射不同药物,记录血压和心率的变化。结果：①L－谷氨酸（Glu)兴奋NVM、P物质（SP）注入背内侧核（NDM）室旁核（NPV）或延髓头端腹外侧区（RVL）均引起升压反应;②NVM升压反应可被双侧NDM、NPV或PVL内预先注射[D-Pro^2,D-Phe^7,D-Trp^9]-P物质（SP拮抗剂）衰减,但RVL内注射阿托品无此效应;③酚妥拉明（i.v.）也能使NVM升压反应减小,而心得安或甲基阿托品（i.v.）对该升压反应无影响。结论：兴奋NVM可通过NDM（SP受体）,作用于NPV（SP受体）升压区和RVL（SP受体）－交感缩血管神经系统产生升压反应。心交感和心迷走神经不参与该反应。     

Comparative characteristic of respiratory pattern responses to kainic acid microinjections in different parts of the nucleus ambiguous

In rats, local chemical isolation of neurones by the kainic acid helped to investigate into comparative role of different parts of the n. ambiguus in respiratory control mechanisms. We disclosed specific peculiarities of responses of rhythm and respiratory pattern to chemical isolation of different parts of the n. ambiguus. In particular, it was found that consecutive isolation of the left and right rostral parts of the n. ambiguus caused a significant decrease of the respiration rate and respiratory volume and also resulted in irreversible cessation of respiration in 83% of experiments. Isolation of symmetric medial parts of the n. ambiguus resulted in bradypnoe and a decrease of pulmonary ventilation; maximal respiratory effect was recorded after kainic acid injection in the symmetric part only, thus the irreversible cessation of respiration was recorded in 50% of experiments. After isolation of symmetric caudal parts of the n. ambiguus we observed an insignificant decrease of the respiration rate without significant changes of the respiratory volume, and number of the respiration cessation was minimal: 33%.     

Involvement of the fastigial nuclei in vagally mediated respiratory responses

Xu, Fadi, and Donald T. Frazier. Involvement of thefastigial nuclei in vagally mediated respiratory responses.J. Appl. Physiol. 82(6):1853-1861, 1997.Previous studies have demonstrated that thecerebellum, especially the fastigial nucleus (FN), is capable ofmodulating respiratory responses to chemical and mechanical stimuli.Because there is evidence to show projections from vagal afferents tothe FN, the goal of this study was to determine the role of the FN inthe respiratory reflexes elicited by activation of vagal afferents.Experiments were performed in anesthetized (chloralose), paralyzed, andartificially ventilated cats with an occipital exposure of thecerebellum. Administration of capsaicin (Cap; 5-10 µg/kg) viathe right external jugular vein at the end of inspiration andapplication of lung inflation (LI; 10 cmH₂O) during inspiration werecarried out to stimulate nonmyelinated and myelinated vagal afferents,respectively. The phrenic neurogram was recorded as anindex of the respiratory motor output. Control cardiorespiratoryvariables [expiratory duration(TE), arterial bloodpressure] and their immediate responses to stimuli were comparedbefore and after bilateral lesions of the FN. The results showed thefollowing. 1) Capinjection and LI resulted in a dramatic increase inTE (apnea).2) FN lesions did not significantlyalter the control TE; however,the apneic duration induced by Cap injection was prolonged.3) Neither FN lesions norcerebellectomy affected the apneic duration that resulted fromapplication of LI. 4) Cold blockadeof the vagi (6-8°C) eliminated the respiratory responses elicited by LI but not Cap injection; vagotomy abolished the responses to both stimuli. 5) FN lesions didnot change the control ABP or its responses to either LI or Capinjection. It is concluded that the FN is involved in vagally mediatedrespiratory reflexes elicited by activation of nonmyelinated (C-fiber)vagal afferents.

     

Cardiac, respiratory, and renal responses to stimulation of the external cuneate nucleus

The cardiac, respiratory, and renal responses of electrical stimulation and microinjection of excitatory amino acids into the external cuneate nucleus were investigated in 57 cats anesthetized with pentobarbital sodium, paralyzed, and artificially ventilated. Trains of rectangular cathodal pulses of 40-100 microA at 50 Hz and 0.1 ms duration were delivered through monopolar glass microelectrodes with a tip diameter of 10-20 micron, filled with indium-Woods metal alloy. Electrical stimulation at 232 histologically identified sites within the external cuneate nucleus could evoke changes in arterial blood pressure, heart rate, and efferent renal sympathetic nerve activity. In a further set of experiments, a change in respiration was observed at 74 identified sites. An increase or decrease in all parameters measured could be elicited at different stimulus sites within the external cuneate nucleus. Repositioning of the electrode (0.2-0.4 mm) in depth or laterally could result in a different response with stimulation. Microinjections of D,L-homocysteic acid or glutamate could mimic the evoked changes in blood pressure, heart rate, efferent renal sympathetic nerve activity, and respiration. This suggests that the external cuneate nucleus contains cell bodies that may modulate components of various cardiac, respiratory and renal reflexes. It is proposed that the external cuneate nucleus may be involved in the integration of somato-autonomic reflex responses.