scholarly journals Midline section of the medulla abolishes inspiratory activity and desynchronizes pre-inspiratory neuron rhythm on both sides of the medulla in newborn rats

2015 ◽  
Vol 113 (7) ◽  
pp. 2871-2878 ◽  
Author(s):  
Hiroshi Onimaru ◽  
Kayo Tsuzawa ◽  
Yoshimi Nakazono ◽  
Wiktor A. Janczewski

Each half of the medulla contains respiratory neurons that constitute two generators that control respiratory rhythm. One generator consists of the inspiratory neurons in the pre-Bötzinger complex (preBötC); the other, the pre-inspiratory (Pre-I) neurons in the parafacial respiratory group (pFRG), rostral to the preBötC. We investigated the contribution of the commissural fibers, connecting the respiratory rhythm generators located on the opposite side of the medulla to the generation of respiratory activity in brain stem-spinal cord preparation from 0- to 1-day-old rats. Pre-I neuron activity and the facial nerve and/or first lumbar (L1) root activity were recorded as indicators of the pFRG-driven rhythm. Fourth cervical ventral root (C4) root and/or hypoglossal (XII) nerve activity were recorded as indicators of preBötC-driven inspiratory activity. We found that a midline section that interrupted crossed fibers rostral to the obex irreversibly eliminated C4 and XII root activity, whereas the Pre-I neurons, facial nerve, and L1 roots remained rhythmically active. The facial and contralateral L1 nerve activities were synchronous, whereas right and left facial (and right and left L1) nerves lost synchrony. Optical recordings demonstrated that pFRG-driven burst activity was preserved after a midline section, whereas the preBötC neurons were no longer rhythmic. We conclude that in newborn rats, crossed excitatory interactions (via commissural fibers) are necessary for the generation of inspiratory bursts but not for the generation of rhythmic Pre-I neuron activity.

1988 ◽  
Vol 65 (6) ◽  
pp. 2498-2505 ◽  
Author(s):  
R. Shannon ◽  
D. C. Bolser ◽  
B. G. Lindsey

Studies were conducted to test the hypothesis that nonrespiratory-modulated units are last-order interneurons mediating the effects of intercostal muscle tendon organs on medullary inspiratory neuron activity. Vagotomized, anesthetized, or decerebrate cats were used. Results show the following. 1) Afferents from different receptor types (i.e., intercostal tendon organs and chest wall cutaneous receptors) that inhibit medullary inspiratory neuron activities evoke the same units. 2) Gastrocnemius muscle group I afferent fibers evoke some of the same units as intercostal afferents but do not alter respiratory activity. 3) The "pneumotaxic center" and laryngeal nerve afferents, which inhibit medullary inspiratory activity, evoke different medullary units than intercostal afferents. 4) Evoked units are not active in spontaneously breathing cats. Additional results suggest that a few respiratory neurons near the retrofacial nucleus may be involved in the mediation of the inspiratory inhibitory effects of intercostal tendon organs. These results do not establish the mechanism by which intercostal muscle tendon organs reduces medullary inspiratory activity.


2006 ◽  
Vol 96 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Hiroshi Onimaru ◽  
Yuko Kumagawa ◽  
Ikuo Homma

There are at least two respiration-related rhythm generators in the medulla: the pre-Bötzinger complex, which produces inspiratory (Insp) neuron bursts, and the parafacial respiratory group (pFRG), which produces predominantly preinspiratory (Pre-I) neuron bursts. The pFRG Pre-I neuron activity has not been correlated with motor neuron activity in slice or block preparations of rostral medulla. In this study, we attempted to detect pFRG Pre-I activity as motor output in the rostral medulla. We recorded respiratory activity of the facial nerve in the brain stem–spinal cord preparation of 0- to 2-day-old rats. Facial nerve activity consisted of preinspiratory, Insp, and postinspiratory activity. Pre- and postinspiratory activity corresponded well with membrane potential trajectories of Pre-I neurons in the rostral ventrolateral medulla. In response to perfusion of 1 μM DAMGO (a μ-opiate agonist), fourth cervical ventral root (C4) Insp activity was depressed and facial nerve activity continued to synchronize with Pre-I neuron bursts. After transverse sectioning between the levels of the pre-Bötzinger complex and the pFRG, C4 Insp activity recovered within 15 min, but facial nerve activity was inhibited. When DAMGO was applied, C4 Insp activity was inhibited, and rhythmic facial nerve activity recovered. Subsequent elevation of K+ concentration reinduced C4 activity, but facial nerve activity was inhibited. Whole cell recordings in the rostral block revealed the presence of putative Pre-I neurons, the activity of which was synchronized with facial nerve activity. These results show that the rostral medulla, not including the pre-Bötzinger complex, produces Pre-I–like rhythmic activity that can be monitored as facial nerve motor output in newborn rat in vitro preparations.


2009 ◽  
Vol 364 (1529) ◽  
pp. 2477-2483 ◽  
Author(s):  
Véronique Dubreuil ◽  
Jacques Barhanin ◽  
Christo Goridis ◽  
Jean-François Brunet

In the last few years, elucidation of the architecture of breathing control centres has reached the cellular level. This has been facilitated by increasing knowledge of the molecular signatures of various classes of hindbrain neurons. Here, we review the advances achieved by studying the homeodomain factor Phox2b , a transcriptional determinant of neuronal identity in the central and peripheral nervous systems. Evidence from human genetics, neurophysiology and mouse reverse genetics converges to implicate a small population of Phox2b -dependent neurons, located in the retrotrapezoid nucleus, in the detection of CO 2 , which is a paramount source of the ‘drive to breathe’. Moreover, the same and other studies suggest that an overlapping or identical neuronal population, the parafacial respiratory group, might contribute to the respiratory rhythm at least in some circumstances, such as for the initiation of breathing following birth. Together with the previously established Phox2b dependency of other respiratory neurons (which we review briefly here), our new data highlight a key role of this transcription factor in setting up the circuits for breathing automaticity.


2007 ◽  
Vol 97 (3) ◽  
pp. 2283-2292 ◽  
Author(s):  
Benjamin J. Barnes ◽  
Chi-Minh Tuong ◽  
Nicholas M. Mellen

In mammals, respiration-modulated networks are distributed rostrocaudally in the ventrolateral quadrant of the medulla. Recent studies have established that in neonate rodents, two spatially separate networks along this column—the parafacial respiratory group (pFRG) and the pre-Bötzinger complex (preBötC)—are hypothesized to be sufficient for respiratory rhythm generation, but little is known about the connectivity within or between these networks. To be able to observe how these networks interact, we have developed a neonate rat medullary tilted sagittal slab, which exposes one column of respiration-modulated neurons on its surface, permitting functional imaging with cellular resolution. Here we examined how respiratory networks responded to hypoxic challenge and opioid-induced depression. At the systems level, the sagittal slab was congruent with more intact preparations: hypoxic challenge led to a significant increase in respiratory period and inspiratory burst amplitude, consistent with gasping. At opioid concentrations sufficient to slow respiration, we observed periods at integer multiples of control, matching quantal slowing. Consistent with single-unit recordings in more intact preparations, respiratory networks were distributed bimodally along the rostrocaudal axis, with respiratory neurons concentrated at the caudal pole of the facial nucleus, and 350 microns caudally, at the level of the pFRG and the preBötC, respectively. Within these regions neurons active during hypoxia- and/or opioid-induced depression were ubiquitous and interdigitated. In particular, contrary to earlier reports, opiate-insensitive neurons were found at the level of the preBötC.


1989 ◽  
Vol 61 (5) ◽  
pp. 918-926 ◽  
Author(s):  
D. C. Bolser ◽  
J. E. Remmers

1. Stimulation of intercostal muscle tendon organs or their afferent fibers reduces medullary inspiratory neuron activity, decreases motor output to inspiratory muscles, and increases the activity of expiratory laryngeal motoneurons. The present study examines the synaptic mechanisms underlying these changes to obtain information about medullary neurons that participate in the afferent limb of this reflex pathway. 2. Membrane potentials of medullary respiratory neurons were recorded in decerebrate paralyzed cats. Postsynaptic potentials (PSPs) elicited in these neurons by intercostal nerve stimulation (INS) were compared before and after intracellular iontophoresis of chloride ions. After chloride injection, the normal hyperpolarization caused by inhibitory (I) PSPs is "reversed" to depolarization. 3. In inspiratory neurons, reversal of IPSPs by chloride injection also reversed hyperpolarization produced by INS when applied during any portion of the respiratory cycle. This observation suggests that increased chloride conductance of the postsynaptic membrane mediated the inhibition. Further, it is very likely that the last-order interneuron in the afferent pathway must be excited by INS and alter inspiratory neuron activity via an inhibitory synapse. The linear relationship between the amplitude of the INS induced PSP and membrane potential of inspiratory neurons provided evidence that neurons in the afferent pathway are not respiratory modulated. 4. The membranes of expiratory vagal motoneurons and post-inspiratory neurons were depolarized by INS during all portions of the respiratory cycle before IPSP reversal. Reversal of IPSPs affected neither this depolarization of expiratory vagal motoneurons during stage I and II expiration nor that of post-inspiratory neurons during stage I expiration. Thus this depolarization probably resulted from synaptic excitation.(ABSTRACT TRUNCATED AT 250 WORDS)


1994 ◽  
Vol 72 (6) ◽  
pp. 2598-2608 ◽  
Author(s):  
S. M. Johnson ◽  
J. C. Smith ◽  
G. D. Funk ◽  
J. L. Feldman

1. We have hypothesized that pacemaker neurons in the pre-Botzinger complex (pre-BotC) form the kernel for respiratory rhythm generation. A prediction of this hypothesis is that oscillatory behavior in some respiratory neurons could persist in the absence of synaptic transmission. In this study we used extracellular recording of neuronal activity in slice preparations from neonatal rat medulla that generate respiratory rhythm in vitro to determine 1) whether pacemaker properties are present in pre-BotC and unique to respiratory neurons, 2) whether pacemaker properties are common to all respiratory neurons, and 3) the spatiotemporal patterns of pacemaker neuron activity. 2. Whole cell recordings from respiratory neurons verified that bathing the slices in a low-Ca2+/high-Mg2+ solution (low-Ca2+ solution) eliminated endogenous respiratory synaptic inputs and electrically evoked synaptic inputs. 3. Sixty-three neurons spontaneously generated rhythmic bursts of action potentials in low-Ca2+ solution. After we switched to control solution to reactivate the respiratory network, these neurons were classified on the basis of their spike discharge patterns relative to the respiratory cycle as: 1) inspiratory (I) neurons (n = 41), 2) tonic expiratory (tonic E) neurons (n = 4), and 3) tonic neurons (n = 18). 4. In other experiments we tested I and tonic E neurons identified first in control solution for bursting behavior in low-Ca2+ solution. Several I neurons (n = 5 of 33), but none of the tonic E neurons (n = 0 of 13), continued to burst rhythmically. 5. Bursting and nonbursting respiratory neurons were distributed throughout the ventrolateral reticular formation within the pre-BotC as well as in the ventral respiratory group (VRG) immediately caudal to the pre-BotC. 6. We conclude that subpopulations of VRG neurons in vitro have rhythmic bursting properties when synaptic transmission is abolished. Respiratory neurons, especially I neurons, were the most prevalent class of bursting cells. Only a small percentage of respiratory neurons, however, had pacemaker properties. These findings are consistent with the hypothesis that the respiratory oscillator includes specialized neurons with intrinsic oscillatory properties.


1987 ◽  
Vol 62 (1) ◽  
pp. 335-343 ◽  
Author(s):  
E. M. Adams ◽  
A. D. Horres ◽  
R. Frayser

The purpose of this study was to describe the distribution and activity pattern of respiratory neurons located in the ventrolateral medulla (VLM) of the dog. Spike activity of 129 respiratory neurons was recorded in 23 ketamine-anesthetized spontaneously breathing dogs. Pontamine blue dye was used to mark the location of each neuron. Most VLM neurons displaying respiratory related spike patterns were located in a column related closely to ambigual and retroambigual nuclei. Both inspiratory and expiratory neurons were present with inspiratory units being grouped more rostrally. The predominant inspiratory neuron firing pattern was “late” inspiratory, although eight “early” types were located. All expiratory firing patterns were the late expiratory variety. Each neuron burst pattern was characterized by determining burst duration (BD), spikes per burst (S/B), peak frequency (PF), time to peak frequency (TPF), rate of rise to peak frequency (PF/TPF), and mean frequency. CO2-induced minute ventilation increases were associated with decreases in BD and TPF and increases in PF, S/B, and PF/TPF. In 11 experiments the relative influences of vagotomy and tracheal occlusion on late inspiratory units were compared. Tracheal occlusion increased late inspiratory BD and S/B but did not alter PF/TPF. Vagotomy increased BD and S/B beyond those obtained by tracheal occlusion and, in some neurons, decreased the PF/TPF. We conclude that the location of respiratory units in the VLM of the dog is similar to that in other species, the discharge pattern of VLM respiratory units is similar to those in cat VLM, and vagotomy and tracheal occlusion affect discharge patterns differently.


1965 ◽  
Vol 43 (3) ◽  
pp. 431-436 ◽  
Author(s):  
M. Samel ◽  
A. Caputa

In newborn rats the mother provokes the emptying of the urinary bladder by stimulating the perineum with her tongue. The possibility that mothers may thereby ingest the urine of their young has been studied by means of 131I on nine litters of rats aged 10 to 29 days. The results indicate that a considerable quantity of 131I administered intraperitoneally to 10- and 18-day-old rats, which were then reunited with their mothers for 4 hours, reappears in the organism of uninjected nurslings after passing through the organism of the mother. The amount of 131I transferred from injected rats into the bodies of isolated uninjected rats of the same litter decreased during the period of weaning. The observed recirculation of 131I between immature rats and their mothers in both directions may represent a saving mechanism which might include several other substances and would compensate for their loss via the milk, and suggests a new aspect of maternal–neonatal interrelationship which appears as a continuation of the state existing in utero.


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