Bulbospinal Research Articles

Changes in respiratory neuronal firing pattern during the hypoxia‐induced transition from eupnea to gasping

Respiratory rhythm is generated in part by medullary neurons in the ventrolateral medulla. The firing patterns of these units during hypoxia-induced state changes are not well characterized. Using arterially-perfused, decerebrated, juvenile rats, we recorded from phrenic motor (PMNs), bulbo-spinal (BSNs), preBötzinger Complex inspiratory, and Bötzinger Complex expiratory neurons during eupnea and anoxia. All recorded units demonstrated an increase in firing rate during the initial hyperpnea (IH) sequence of the anoxic test. About one-half of PMNs and BSNs continued their discharges through various anoxia-induced state changes, including gasping. By contrast, expiratory augmenting neurons were completely silent at the end of IH. Approximately one-third of post-inspiratory neurons were relatively resistant to anoxia. Almost one-half of pre-inspiratory/inspiratory neurons were also resistant to anoxia, demonstrating increasing firing rate and duration of the pre-inspiratory component during transition between IH and gasping. About one-third of all inspiratory-augmenting units showed irregular activity during the transition from IH to gasping, including changes to an inspiratory-decrementing pattern during gasping. Our data suggest a more complex respiratory network reconfiguration during the hypoxia-induced transition from eupnea to gasping than has been previously described.

Neurokinin-1 receptor-expressing cells of the ventral respiratory group are functionally heterogeneous and predominantly glutamatergic.

According to a recent theory (Gray et al., 1999) the neurokinin-1 receptor (NK1R)-immunoreactive (ir) neurons of the ventral respiratory group (VRG) are confined to the pre-Bötzinger complex (pre-BötC) and might be glutamatergic interneurons that drive respiratory rhythmogenesis. In this study we tested whether the NK1R-ir neurons of the VRG are glutamatergic. We also examined whether different groups of NK1R-ir neurons coexist in the VRG on the basis of whether these cells contain preproenkephalin (PPE) mRNA or project to the spinal cord. NK1R immunoreactivity was found in two populations of VRG neurons that are both predominantly glutamatergic because most of them contained vesicular glutamate transporter 2 mRNA (77 +/- 9%; n = 3). A group of small fusiform neurons (somatic cross section: 91 +/- 3.6 microm2) that has neither PPE mRNA nor spinal projections is primarily restricted to the pre-BötC. These cells may be the interneurons the destruction of which produces massive disruptions of the respiratory rhythm (Gray et al., 2001). The rest of the NK1R-ir neurons of the VRG are multipolar, are larger (somatic cross section: 252 +/- 15 microm2), and express high levels of PPE mRNA. Some of these cells located in the rostral half of the rostral VRG project to the spinal cord (C4 or T3). Using electrophysiological methods, we showed that these bulbospinal NK1R-ir neurons are slowly discharging inspiratory-augmenting neurons, suggesting that they may control phrenic or intercostal motor neurons. In summary, NK1R-expressing cells of the VRG are a heterogeneous group of predominantly glutamatergic neurons that include subpopulations of respiratory premotor neurons.

Regulation of sympathetic tone and arterial pressure by the rostral ventrolateral medulla after depletion of C1 cells in rats.

This review describes experiments designed to determine the role of bulbospinal (BS) C1 cells in regulating the sympathetic outflow and blood pressure. This goal was achieved by analyzing the physiological consequences of destroying BS C1 cells. These cells were destroyed by suicide transport of an anti-dopamine-beta-hydroxylase antibody conjugated to saporin (anti-D beta H-SAP). Two to 3 weeks after spinal cord injection (T2-T6), the toxin destroyed 75-85% of BS C1 and C3 cells along with > 95% of BS noradrenergic neurons (A5, A6, A7). The toxin spared BS noncatecholaminergic cells. Under anesthesia, toxin-treated rats had a normal blood pressure and an apparently normal sympathetic nerve discharge (SNA, splanchnic), and intravenous clonidine caused a normal degree of sympathoinhibition. Inhibition of rostral ventrolateral medulla (RVLM) neurons by bilateral injection of muscimol caused the same hypotension and sympathoinhibition as in control rats. The baroreflex range was 41% attenuated by the toxin, but the MAP50 was unchanged. Sympathoexcitatory responses to stimulation of peripheral chemoreceptors with cyanide or to electrical stimulation of RVLM were severely depressed (60% to 80%) in toxin-treated rats. Rats in which A5 neurons were selectively destroyed had no deficit in the parameters tested. Unit recordings of BS RVLM neurons indicated that the toxin destroyed most barosensitive C1 neurons, but spared noncatecholaminergic lightly myelinated BS cells. In summary, the integrity of C1 neurons is not essential for the generation of SNA and the maintenance of BP under resting conditions, perhaps because these functions are performed primarily by noncatecholaminergic BS neurons. However, the deficits caused by treatment with anti-D beta H-SAP indicate that BS C1 neurons play a crucial role in several sympathoexcitatory responses mediated by the RVLM.

Bulbospinal neurons of the cat that co-contain serotonin and methionine enkephalin.

The present study utilizes a combined retrograde transport of Fast Blue (or rhodamine-labeled latex microspheres) and simultaneous immunofluorescence technique to demonstrate directly the coexistence of serotonin and methionine enkephalin in bulbospinal neurons of the cat. The bulbospinal neurons that immunostained for both serotonin and enkephalin were observed, without any distinct somatotopic organization, in the nuclei raphe pallidus, obscurus and magnus. They were also observed in the nucleus reticularis magnocellularis and the ventrolateral medulla (cell group B1/3). Among the bulbospinal neurons encountered within individual 5-HT-rich medullary nuclei, high proportions of these neurons co-containing serotonin and methionine enkephalin were evidenced in the nucleus raphe obscurus (64%) and nucleus raphe pallidus (56%), less so in cell group B1/3 (41%), nucleus raphe magnus (39%), and the nucleus reticularis magnocellularis (29%). Physiological significance of such a morphological substrate is discussed.

Influence of trigeminal nasal afferents on bulbar respiratory neuronal activity

This study examined the influence of nasal trigeminal afferents, the anterior ethmoidal nerve (AEN) and posterior nasal nerves (PNN) on the spike discharges of respiratory-related neurons recorded in the ventral respiratory group (VRG) (2.6–3.5 mm lateral to the midline, from 1 mm rostral to 3 mm caudal to the obex and at depth of 2–4 mm below the dorsal surface). Electrical stimulations to the AEN and PNN were administered to 10 pentobarbital anaesthetized cats and to 8 ketamine anaesthetized, vagotomized, curarized and ventilated cats. Single shock stimulations of either nerve evoked transient and total inhibition of inspiratory activities. Expiratory-related neurons of the VRG presented three patterns of activity in response to stimulation:excitation, inhibition or inhibition followed by excitation. More generally, expiratory units are activated with a short latency. In the course of repetitive stimulation of the AEN and PNN we observed a prolongation of the spontaneous inspiratory discharge which presented transient, short inhibition in response to each shock. Most expiratory units presented a short activation which was synchronous with the transient inhibition of inspiratory activities. When repetitive stimulation provoked a sneeze-like response, we observed a progressive increase in the duration of transient inspiratory inhibition first, associated with a progressive reinforcement of transient expiratory activation. Secondarily, just before the expiratory thrust, we noted a stronger inhibition of the inspiratory activity which preceded a high-frequency (400 Hz) expiratory discharge. Nasal afferents exert a forceful excitatory effect on bulbospinal (BS) and non-bulbospinal—non-vagal (NBS-NV) expiratory cells of the VRG. The effects due to vagotomy and curarization are discussed.

Historical development of current concepts on central chemosensitivity.

The history of concepts on the mechanism of central chemosensitivity is reviewed with special emphasis on ideas that have remained valid or stimulating until today. Early physiologists considered chemoreception to be a property of respiratory neurones in the brainstem (Pflüger 1868; Gesell 1926, 1949; Winterstein 1910, 1921, 1956). It has not been elucidated by which mechanism acid/base disturbances cause cardiorespiratory adaption. The reaction theory focused on protons as being the decisive stimulus (Lehmann 1888, Winterstein 1921, Loeschcke 1982), but this issue can be adequately discussed only when the compartment where changes occur is taken into account (Jacobs 1920, Gesell 1940). Heymans and collaborators demonstrated in 1930 that chemoreception is not only possible by a central mechanism but also at the level of the peripheral chemoreceptors. Without solid evidence for such an assumption, the existence of specific 'receptors' for pH and/or pCO2 was postulated by von Euler and Söderberg in 1952. Several chemosensitive areas at the ventrolateral surface of the medulla oblongata were defined by Loeschcke and collaborators in a series of papers after 1958. Within these areas, however, a specific chemoreceptor has not been distinguished. On the other hand, a direct chemosensitivity of bulbospinal sympathoexcitatory neurones as an intrinsic property of these neurones has recently been demonstrated (Seller 1989). Therefore, coming back to the original concept of chemoreception as a function of central cardio-respiratory neurones appears to be the most promising path for future research.

Responses of bulbospinal neurons during expiration reflex in cats

The responses of 129 bulbospinal (BS) neurons were investigated an anesthetized cats during the expiration reflex evoked by mechanical stimulation of the vocal folds or electrostimulation of the superior laryngeal nerve. It was found that in addition to expiratory and inspiratory neurons, a large number of nonrespiratory BS cells localized bilaterially, primarily in the giant-cell tegmental fields, are activated. It is shown that expulsive expiration during this reflex is to a considerable extent provided by activation of non-respiratory BS neurons participating also in the transmission of descending influences from high-threshold afferents of other modalities.

Motor recovery after serial spinal cord lesions of defined descending pathways in cats

The food-taking movement by which a cat uses its forepaw to take a piece of food and bring it to its mouth normally depends on the cortico- (CS) and rubrospinal (RS) tracts and disappears when they are transected in C5; a slow reappearance over months is due to bulbospinal (BS) take-over. After complete CS transection but minimal RS transection, food-taking remains. If, one month later, the RS tract is completely transected, food-taking is not abolished as it is when transection is made in one session. It is permanently abolished after a third transection of the ventral quadrant in C2. It is suggested that the food-taking remaining after the first lesion is due to combined RS and BS activity and that the RS tract induces the BS neurones to contribute to the extent that they can take over when the RS tract is completely transected.

Morphological and electrical description of medullary respiratory neurons of the cat.

The activity of 32 respiratory neurons located within the retroambigual region of the lower brain stem was recorded intracellulary and the neurons were stained using Procion Yellow. Inspiratory and expiratory bulbospinal (BS), vagal (V) neurons were identified by stimulation within the ventrolateral portions of the cervical spinal cord and the vagal nerves. Another group of inspiratory and expiratory neurons was not antidromically activated by such stimulations (NAA-neurons).

Role of the reticular formation in the elaboration of bulbo-spinal discharges of somatesthetic origin in the cat under chloralose

Role of the reticular formation in the elaboration of bulbo-spinal discharges of somatesthetic origin in the cat under chloralose