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.     

Medullary lateral tegmental field neurons influence the timing and pattern of phrenic nerve activity in cats.

In an effort to characterize the role of the medullary lateral tegmental field (LTF) in regulating respiration, we tested the effects of selective blockade of excitatory (EAA) and inhibitory amino acid (IAA) receptors in this region on phrenic nerve activity (PNA) of vagus-intact and vagotomized cats anesthetized with dial-urethane. We found distinct patterns of changes in central respiratory rate, duration of inspiratory and expiratory phases of PNA (Ti and Te, respectively), and I-burst amplitude after selective blockade of EAA and IAA receptors in the LTF. First, blockade of N-methyl-D-aspartate (NMDA) receptors significantly (P < 0.05) decreased central respiratory rate primarily by increasing Ti but did not alter I-burst amplitude. Second, blockade of non-NMDA receptors significantly reduced I-burst amplitude without affecting central respiratory rate. Third, blockade of GABAA receptors significantly decreased central respiratory rate by increasing Te and significantly reduced I-burst amplitude. Fourth, blockade of glycine receptors significantly decreased central respiratory rate by causing proportional increases in Ti and Te and significantly reduced I-burst amplitude. These changes in PNA were markedly different from those produced by blockade of EAA or IAA receptors in the pre-B?tzinger complex. We propose that a proper balance of excitatory and inhibitory inputs to several functionally distinct pools of LTF neurons is essential for maintaining the normal pattern of PNA in anesthetized cats.     

Kainic acid lesions to the lateral tegmental field of medulla: effects on cough, expiration and aspiration reflexes in anesthetized cats

We have tested the hypothesis that neurons of both the ventral reticular nucleus and the adjacent parts of the lateral tegmental field (LTF) may be important for the production of motor programs associated with cough, expiration and aspiration reflexes. Our studies were conducted on non-decerebrate, spontaneously breathing cats under pentobarbitone anesthesia. Dysfunction of the medullary LTF region above the obex, produced by uni- or bilateral injections of kainic acid (a neurotoxin), regularly abolished the cough reflex evoked by mechanical stimulation of both the tracheobronchial and laryngeal regions and in most cases also the expiration reflex induced from the glottal area. However, some electrical activity still occurred in the neurogram of the recurrent laryngeal nerve during probing the laryngeal and glottal regions. Interestingly, the aspiration reflex elicited from the nasopharynx regularly persisted, although with lower intensity after the LTF lesion. Nevertheless, successive midcollicular decerebration performed in four cats also abolished the aspiration reflex. These experiments demonstrate the importance of medullary LTF neurons for the normal occurrence of cough and expiration reflexes. One possible explanation for the elimination of these expulsive processes is that the blockade of the LTF neurons may remove an important source of a facilitatory input to the brainstem circuitries that mediate cough and expiration reflexes. In addition, the potential importance of the mesencephalic reticular formation for the occurrence of the aspiration reflex and the role of the LTF in modulating both the eupnoeic breathing and the blood pressure are also discussed.     

Role of lateral geniculate neurons in color discrimination in cats

Responses of 43 lateral geniculate neurons to stimulation by flashes of different wavelengths were studied in cats. The neurons were divided into two groups. The first group (44%) gave high-frequency spike discharges which were unaltered by a change in stimulus wavelength. The second group (51%) responded differently to different colors. Statistically significant differences were found in their responses to flashes of different wavelengths. A possible inhibitory influence of the first group of neurons on the second group was demonstrated and its possible significance for color vision is discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 11, No. 3, pp. 195–200, May–June, 1979.     

Medullary lateral tegmental field: an important source of basal sympathetic nerve discharge in the cat

We used blockade of excitatory amino acid (EAA) neurotransmission in the medullary lateral tegmental field (LTF) and rostral ventrolateral medulla (RVLM) to assess the roles of these regions in the control of inferior cardiac sympathetic nerve discharge (SND) and mean arterial pressure (MAP) in urethan-anesthetized, baroreceptor-denervated cats. Bilateral microinjection of a non-N-methyl-D-aspartate (NMDA)-receptor antagonist [1,2,3, 4-tetrahydro-6-nitro-2,3-dioxobenzo-[f]quinoxaline-7-sulfonamide (NBQX)] into the LTF significantly decreased SND to 46 +/- 4% of control (as demonstrated with power-density spectral analysis) and MAP by 16 +/- 6 mmHg. In contrast, bilateral microinjection of an NMDA-receptor antagonist [D(-)-2-amino-5-phosphonopentanoic acid (D-AP5)] into the LTF did not decrease SND or MAP. These results demonstrate that the LTF is an important synaptic relay in the pathway responsible for basal SND in the cat. Bilateral microinjection of NBQX or D-AP5 into the RVLM significantly decreased power in SND to 48 +/- 5 or 61 +/- 5% of control, respectively, and reduced MAP by 15 +/- 2 or 8 +/- 4 mmHg, respectively. These data indicate that EAA-mediated synaptic drive to RVLM-spinal sympathoexcitatory neurons accounts for a significant component of their basal activity.     

Medullary lateral tegmental field mediates the cardiovascular but not respiratory component of the Bezold-Jarisch reflex in the cat

We determined the effects of bilateral microinjection of muscimol and excitatory amino acid receptor antagonists into the medullary lateral tegmental field (LTF) on changes in sympathetic nerve discharge (SND), mean arterial pressure (MAP), and phrenic nerve activity (PNA; artificially ventilated cats) or intratracheal pressure (spontaneously breathing cats) elicited by right atrial administration of phenylbiguanide (PBG; i.e., the Bezold-Jarisch reflex) in dial-urethane anesthetized cats. The PBG-induced depressor response (-66 +/- 8 mmHg; mean +/- SE) was converted to a pressor response after muscimol microinjection in two of three spontaneously breathing cats and was markedly reduced in the other cat; however, the duration of apnea (20 +/- 3 vs. 17 +/- 7 s) was essentially unchanged. In seven paralyzed, artificially ventilated cats, muscimol microinjection significantly (P < 0.05) attenuated the PBG-induced fall in MAP (-39 +/- 7 vs. -4 +/- 4 mmHg) and the magnitude (-98 +/- 1 vs. -35 +/- 13%) and duration (15 +/- 2 vs. 3 +/- 2 s) of the sympathoinhibitory response. In contrast, the PBG-induced inhibition of PNA was unaffected (3 cats). Similar results were obtained by microinjection of an N-methyl-D-aspartate (NMDA) receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, into the LTF. In contrast, neither the cardiovascular nor respiratory responses to PBG were altered by blockade of non-NMDA receptors with 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide. We conclude that the LTF subserves a critical role in mediating the sympathetic and cardiovascular components of the Bezold-Jarisch reflex. Moreover, these data show separation of the pathways mediating the respiratory and cardiovascular responses of this reflex at a level central to bulbospinal outflows to phrenic motoneurons and preganglionic sympathetic neurons.     

Dynamic and static receptive field characteristics of single neurons in the lateral suprasylvian area in cats

Static and dynamic properties of receptive fields of neurons in the lateral suprasylvian area of the cat cerebral cortex were studied. Neurons with different dynamic characteristics may have an identical static organization of their receptive fields; strict correlation is thus not found between these two characteristics of neurons in this area. Most black-sensitive neurons were found to have a receptive field with off-response. Stimulus contrast reversal tests showed that generation of responses to presentation of both black and light stimuli takes place as a result of excitation of the same area of the receptive field and is not due to spatially different on- and off-zones.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 116–123, January–February, 1984.     

Role of glutamate in the rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation

Visceral sympathoexcitatory reflexes induced by stimulation of the gallbladder with bradykinin (BK) are attenuated by electroacupuncture (EA) at Neiguan-Jianshi (P5-6) acupoints located over the median nerve. Previous studies have shown that neurons in the rostral ventrolateral medulla (rVLM) receive convergent input from visceral organs and somatic nerves (activated by EA). Glutamate (Glu), an important excitatory neurotransmitter in the rVLM, processes visceral sympathoexcitatory cardiovascular reflexes. In the present study, we determined the relation between EA-mediated opioidergic modulation of visceral cardiovascular responses and Glu. Reflex cardiovascular responses were evoked by application of BK to the gallbladder before and after EA in anesthetized cats. Glu concentrations ([Glu]) were measured by HPLC from samples collected by microdialysis probe(s) inserted unilaterally or bilaterally into the rVLM. BK-induced reflex responses and [Glu] were attenuated by 45% and 70%, respectively, after 30 min of EA (n = 6). EA alone did not change [Glu] in the rVLM (n = 6, P > 0.05). However, microdialysis of naloxone (100 mM) into the rVLM reversed EA-related inhibition of blood pressure and [Glu] (n = 5). Immunohistochemical visualization showed that delta-opioid receptors colocalized with, and were in close apposition to, vesicular Glu transporter 3- and c-Fos-double-labeled perikarya and processes of rVLM neurons after gallbladder stimulation with BK. These data suggest that EA attenuates BK-induced visceral sympathoexcitatory reflexes through opioid-mediated inhibition of Glu's action in the rVLM.     

Role of medullary GABA, opioids, and nociceptin in prolonged inhibition of cardiovascular sympathoexcitatory reflexes during electroacupuncture in cats

Electroacupuncture (EA) causes prolonged suppression of reflex elevations in blood pressure for 1-2 h in anesthetized preparations. A long-loop pathway involving the arcuate nucleus (ARC), ventrolateral periaqueductal gray, and rostral ventrolateral medulla (rVLM) is involved in sympathoinhibitory cardiovascular EA effects. However, the mechanisms and locations of the prolonged EA inhibition are unknown. We hypothesized that this effect is mediated through a long-loop pathway involving opioid, nociceptin, and gamma-aminobutyric acid (GABA) receptor activation in the rVLM. In anesthetized, ventilated cats application of bradykinin to the gallbladder every 10 min induced consistent reflex increases in blood pressure. Bilateral EA stimulation at the cardiovascular acupoints P5-6 overlying the median nerves reduced the reflex responses for at least 80 min. Bilateral blockade with kynurenic acid in the ARC 60 min after onset of EA inhibition reversed the cardiovascular response, suggesting a role for the ARC in the long-loop pathway during the prolonged inhibitory response. Unilateral microinjection with either an opioid or a GABA(A) antagonist in rVLM 50-60 min after the beginning of the EA response reversed EA inhibition of the cardiovascular excitatory reflex. Gabazine also reversed EA inhibition of cardiovascular premotor sympathetic rVLM neurons. Conversely, microinjection of a nociceptin/orphanin FQ peptide antagonist did not affect the prolonged inhibitory effect. Thus the ARC, an important component in the long-loop pathway in the EA cardiovascular response, is required for prolonged suppression of reflex cardiovascular excitatory responses by EA. Furthermore, in the rVLM, opioids and GABA, but not nociceptin, participate in the long-term EA-related inhibition of sympathoexcitatory cardiovascular responses.     

Transcriptional and functional divergence in lateral hypothalamic glutamate neurons projecting to the lateral habenula and ventral tegmental area

1. Download : Download high-res image (200KB)
2. Download : Download full-size image

     

Medullary lateral tegmental field: control of respiratory rate and vagal lung inflation afferent influences on sympathetic nerve discharge

We used spectral analysis and event-triggered averaging to determine the effects of chemical inactivation of the medullary lateral tegmental field (LTF) on 1) the relationship of intratracheal pressure (ITP, an index of vagal lung inflation afferent activity) to sympathetic nerve discharge (SND) and phrenic nerve activity (PNA) and 2) central respiratory rate in paralyzed, artificially ventilated dial-urethane-anesthetized cats. ITP-SND coherence value at the frequency of artificial ventilation was significantly (P<0.05; n=18) reduced from 0.73+/-0.04 (mean+/-SE) to 0.24+/-0.04 after bilateral microinjection of muscimol into the LTF. Central respiratory rate was unexpectedly increased in 12 of these experiments (0.28+/-0.03 vs. 0.95+/-0.25 Hz). The ITP-PNA coherence value was variably affected by chemical inactivation of the LTF. It was unchanged when central respiratory rate was also not altered, decreased when respiratory rate was increased above the rate of artificial ventilation, and increased when respiratory rate was raised from a value below the rate of artificial ventilation to the same frequency as the ventilator. Chemical inactivation of the LTF increased central respiratory rate in four of six vagotomized cats but did not significantly affect the PNA-SND coherence value. These data demonstrate that the LTF 1) plays a critical role in mediating the effects of vagal lung inflation afferents on SND but not PNA, 2) helps maintain central respiratory rate in the physiological range, but 3) is not involved in the coupling of central respiratory and sympathetic circuits.     

Role of the arterial baroreflex in 5-HT1A receptor agonist-mediated sympathoexcitation following hypotensive hemorrhage

5-HT1A-receptor agonists rapidly restore blood pressure and sympathetic activity in conscious rats subjected to hypotensive hemorrhage. 5-HT1A-receptor activation has also been shown to produce a robust increase in baroreceptor-dependent, pulse-synchronous firing of cardiac sympathetic nerves in anesthetized cats. To determine whether 5-HT1A-receptor agonists reverse hemorrhage-induced suppression of sympathetic activity through facilitation of the arterial baroreflex, the effects of the 5-HT1A-receptor agonist, 8-OH-DPAT, were assessed in male Sprague-Dawley rats subjected to sinoaortic baroreceptor denervation and subsequent hypotensive hemorrhage. 8-OH-DPAT produced rapid pressor and sympathoexcitatory responses in hemorrhaged animals that were attenuated, but not blocked, by sinoaortic denervation (SAD) (+49 +/- 4 vs. +37 +/- 4 mmHg; +165 +/- 30 vs. +92 +/- 24% baseline, P < 0.01). Spectral analysis of sympathetic activity showed that SAD abolished the 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT)-mediated increases in pulse-synchronous (13 +/- 1 vs. 5 +/- 1% total power for intact vs. SAD rats, P < 0.01) and Mayer wave-related bursting (18 +/- 3 vs. 8 +/- 1% total power, P < 0.05). However, 8-OH-DPAT continued to increase total power (+72 +/- 22 vs. -63 +/- 7% prehemorrhage total power, P < 0.05) and power at the respiratory frequency (35 +/- 2 vs. 25 +/- 4% total power) in SAD animals. These data indicate that full expression of the sympathoexcitatory effect of 8-OH-DPAT requires a functional arterial baroreflex. However, a portion of the effect is due to activation of arterial baroreflex-independent sympathetic pathways.     

Two types of P neurons in the medullary dorsal respiratory cellular group in cats

Electrophysiological properties of P neurons localized in the medullary dorsal respiratory cellular group and of vagal afferent fibers innervating these neurons were studied in acute experiments on nembutal-anesthetized cats with preserved spontaneous respiration. P neurons were shown to form a non-homogeneous cellular population. They generated phasic discharges during the whole inspiration period, but differed in their responses to lung inflation. These findings allowed us to classify P neurons as slowly adapting and rapidly adapting units, probably activated by slowly and rapidly adapting pulmonary receptors, respectively. Sensitivity of the slowly adapting P neurons to activation by the corresponding receptors and the mechanisms underlying the participation of the two types of P neurons in the reflex feedback between the respiratory center and lungs are discussed.Neirofiziologiya/Neurophysiology, Vol. 26, No. 3, pp. 211–217, May–June, 1994.     

Role of the lateral hypothalamus in sleep

Sleep and Biological Rhythms -     

Responses of medullary neurons to microstimulation of the "locomotor strip" in cats

Synaptic responses of medullary neurons to stimulation of the bulbar locomotor strip with a current of about 20 µA were studied by an extracellular recording method in mesencephalic cerebellectomized cats. The mean latent period of response of 177 neurons was 3.2 msec. Neurons in which synaptic responses appeared were located in both the lateral and the medial parts of the reticular formation, but short-latency responses were recorded predominantly in the lateral part. In response to a single stimulus 32% of neurons generated a discharge of 2–4 spikes. "Respiratory" neurons were not excited by stimulation of the locomotor point. The results indicate that neurons of the locomotor strip may have an excitatory action not only on each other, but also on neurons located medially. The possible mechanisms of the spread of activity to the superior cervical segments of the spinal cord are discussed.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 3, pp. 275–282, May–June, 1981.     

延髓腹外侧区在降压反射中的作和

在各种心血管反射中,降压反射是最主要的,延髓腹外侧区在降压反射中起重要作用,目前认为降压反射中枢通路中至少有四种成分是最基本的：（１）孤束核中的神经元;（２）延髓腹外侧头端的交感前运动细胞;（３）延髓腹外侧尾端;（４）疑核或／和迷走神经背运动核。此外,兴奋性与抑制性氨基酸受体和抑制性神经元也是中枢通路的关键成分,下丘脑视上核与室旁核的升压素分泌细胞也有一定作用。