Medulla Of Brainstem-spinal Cord Preparation Research Articles

Postnatal developmental changes in activation profiles of the respiratory neuronal network in the rat ventral medulla

Two putative respiratory rhythm generators (RRGs), the para-facial respiratory group (pFRG) and the pre-Bötzinger complex (preBötC), have been identified in the neonatal rodent brainstem. To elucidate their functional roles during the neonatal period, we evaluated developmental changes of these RRGs by optical imaging using a voltage-sensitive dye. Optical signals, recorded from the ventral medulla of brainstem-spinal cord preparations of neonatal (P0-P4) rats (n = 44), were analysed by a cross correlation method. With development during the first few postnatal days, the respiratory-related activity in the pFRG reduced and shifted from a preinspiratory (P0-P1) to an inspiratory (P2-P4) pattern, whereas preBötC activity remained unchanged. The mu-opioid agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) augmented preinspiratory activity in the pFRG, while the mu-opioid antagonist naloxone induced changes in spatiotemporal activation profiles that closely mimicked the developmental changes. These results are consistent with the recently proposed hypothesis by Janczewski and Feldman that the pFRG is activated to compensate for the depression of the preBötC by perinatal opiate surge. We conclude that significant reorganization of the respiratory neuronal network, characterized by a reduction of preinspiratory activity in the pFRG, occurs at P1-P2 in rats. The changes in spatiotemporal activation profiles of the pFRG neurones may reflect changes in the mode of coupling of the two respiratory rhythm generators.

Point:Counterpoint: The parafacial respiratory group (pFRG)/pre-Bötzinger complex (preBötC) is the primary site of respiratory rhythm generation in the mammal

Point:Counterpoint: The parafacial respiratory group (pFRG)/pre-Bötzinger complex (preBötC) is the primary site of respiratory rhythm generation in the mammal

Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats.

In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst-generating properties of preinspiratory (Pre-I) neurons in the rostral ventrolateral medulla, which have been suggested to be primary respiratory rhythm-generating neurons, were studied by "perforated" whole-cell recordings using the antibiotic nystatin. Nystatin causes small pores to be formed in the cells, through which pass small monovalent ions. For blockade of chemical synaptic transmission, perfusate Ca2+ concentration was lowered to 0.2 mM and the Mg2+ concentration was increased to 5 mM. In low-Ca2+, high-Mg2+ solution (referred to here as "low Ca"), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type), 14 fired tonically (tonic type), and 31 were silent (silent type). Burst-type neurons showed periodic depolarization of 5-12 mV in low Ca, at a rate of 12 +/- 6.5/min. Hyperpolarization of the membrane caused decrease in or disappearance of the periodic depolarization and prolongation of the cycle period. Thus, the burst generations were voltage dependent. The firing frequency of tonic-type neurons was 2.3 +/- 1.6 Hz and was decreased by hyperpolarization. In 6 of these neurons, the firing patterns changed to burst patterns during continuous hyperpolarization. Membrane depolarization by continuous outward current injection into some silent-type neurons (3 of 11 tested) induced bursting activity. Activity of C4 and Pre-I neurons was completely silent with 0.1-1 microM tetrodotoxin (TTX) added to the standard perfusate. In low Ca, burst-type neurons (n = 3) were also silent with 1 microM TTX perfusion. Inspiratory neurons either became silent (n = 4) or fired tonically (n = 1) in low Ca. The present study by "perforated" whole-cell recordings confirmed that some Pre-I neurons possess intrinsic burst-generating properties, which were not attributable to phasic synaptic inputs.

Correlation analysis of respiratory neuron activity in ventrolateral medulla of brainstem-spinal cord preparation isolated from newborn rat.

Cross-correlation analysis was used to study functional connections between one inspiratory (I) neuron and another, and between one pre-inspiratory (Pre-I) neuron and another, in 54 brainstem-spinal cord preparations isolated from newborn rats. Pre-I neurons usually fired in the pre- and post-inspiratory phases. Neurons were recorded extracellularly with pairs of microelectrodes placed on the same or opposite sides of the brainstem. Fourteen pairs of Pre-I neurons recorded bilaterally in the rostral ventrolateral medulla (RVL), 14 pairs of ipsilateral Pre-I neurons in the RVL, 14 pairs of bilateral I neurons in the RVL and 12 pairs of ipsilateral I neurons in the ventrolateral medulla were studied. Cross-correlation histograms (CCHs) were computed. Significantly high peak bin counts were detected in 24 of 54 pairs. Peaks on one side of the origin of the CCHs were observed for one pair of ipsilateral Pre-I neurons, four pairs of bilateral I neurons and five pairs of ipsilateral I neurons. These findings suggest mono- or oligo-synaptic excitatory connections between paired neurons or shared inputs. Only one trough suggesting an oligo-synaptic inhibitory connection was evident in a CCH obtained from the pair of bilateral I neurons. This CCH revealed the peak and the trough on opposite sides of the origin, which was consistent with reciprocal excitatory and inhibitory connections between recorded neurons. Peaks on both sides of the origin were observed for three pairs of bilateral I neurons. From auto-correlation analysis and the latencies of these peaks, two of the three CCHs were consistent with reciprocal excitatory connections between recorded neurons, whereas the other CCH suggests shared inputs. Peaks at the origin were observed for two pairs of ipsilateral Pre-I neurons, four pairs of bilateral I neurons and five pairs of ipsilateral I neurons. These results suggest shared inputs. For Pre-I neurons recorded in opposite sides, no significant bin counts were detected. Peaks on one side were detected for three pairs. Present results suggest short-term synchronisation of I neurons, and of Pre-I neurons via excitatory coupling, and the likelihood of comparatively strong interaction between I neurons, which may be important in maintaining the I burst.

Possible mutual excitatory couplings between inspiratory neurons in caudal ventrolateral medulla of brainstem-spinal cord preparation isolated from newborn rat

In in vitro brainstem-spinal cord preparations, projection of inspiratory neurons in the caudal ventrolateral medulla (CVL) was examined electrophysiologically, and connectivity between bilateral inspiratory neurons in the CVL was analyzed by pulse-cross correlation (PCC) analysis. CVL inspiratory neurons were found to project to the contralateral CVL and/or mainly ipsilateral spinal cord. PCC analysis revealed significant peaks with different latency on both sides of time zero in 3 of 8 pairs. Results were consistent with mono- or oligo-synaptic excitatory connections between bilateral inspiratory neurons in the CVL.

Whole cell recordings from respiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats

In brainstem-spinal cord preparations isolated from newborn rats, a whole cell recording technique was applied to record membrane potentials of inspiratory (Insp) and pre-inspiratory (Pre-I) neurons in the ventrolateral medulla. Labelling of these respiratory neurons with Lucifer Yellow allowed analysis of their locations and morphology. Intracellular membrane potentials from 25 Insp neurons were recorded. Average resting membrane potential was -49 mV (n = 25) and input resistance was 306 M omega. Insp neurons were classified into three types from the patterns of synaptic potentials. Type I neurons (n = 11) had a high probability of excitatory postsynaptic potentials (EPSPs) in the pre- and post-inspiratory phases. Type II neurons (n = 7) showed abrupt transition to the burst phase from the resting potential level without increased EPSPs in the preinspiratory phase. Type III neurons (n = 7) were hyperpolarized by inhibitory postsynaptic potentials (IPSPs) in the pre- and post-inspiratory phases. These Insp neurons, located in the ventrolateral medulla 80-490 microns from the ventral surface, were 10-30 microns in diameter, and had various soma shapes (pyramidal, spherical or fusiform). Intracellular membrane potentials from 24 Pre-I neurons were recorded. The average resting membrane potential was -45 mV (n = 24), and the input resistance was 320 M omega. Typical Pre-I neurons showed fairly great depolarization accompanied by action potentials during their burst phase and repolarization during the inspiratory phase. Most Pre-I neurons appeared to have a high level of synaptic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Whole cell recordings of respiratory neurons in ventrolateral medulla of brainstem-spinal cord preparation in vitro

Whole cell recordings of respiratory neurons in ventrolateral medulla of brainstem-spinal cord preparation in vitro

Primary respiratory rhythm generator in the medulla of brainstem-spinal cord preparation from newborn rat

It has been previously demonstrated that rhythmically firing neurons (Pre-I neurons) preceding cervical root (C 4 or C 5) inspiratory activity, localized in the rostral ventrolateral medulla (RVL), are important in the generation of the basic respiratory rhythm in brainstem-spinal cord preparations from newborn rats. We examined the effects of single and continuous electrical stimulation applied to the RVL on Pre-I and C 4 activities in these preparations. We verified that the phase of respiratory rhythm was reset when Pre-I firing was induced in both right and left RVL by single shock stimulation, whether C 4 activity appeared or not. Lower frequency and intensity of continuous pulse train stimulation in the RVL enhanced Pre-I activity, and hence C 4 activity, whereas higher frequency and intensity inhibited both. The results suggest that synchronous burst activity between the right and left Pre-I neurons must be above a certain level (in its intraburst firing rate) to trigger C 4 inspiratory activity and, therefore, that cooperation among Pre-I neurons is important for induction of rhythmic inspiratory drive. After bilateral lesions of the caudal ventrolateral medulla, Pre-I neurons retained their rhythmic activity, while C 4 activity disappeared. Present results further confirmed our hypothesis that Pre-I neurons are the primary generator of respiratory rhythm. We propose a hypothetical model of the generation of rhythmic respiratory activity.

Localization of respiratory rhythm-generating neurons in the medulla of brainstem-spinal cord preparations from newborn rats

We describe the location of Pre-I neurons, which are important to respiratory rhythm generation, in the rostral medulla of brainstem-spinal cord preparations isolated from newborn rats. This neuronal group was delimited in the reticular formation slightly medial to the caudal area of the facial nucleus and near the ventral surface. The effects of electrical stimulation and lesions in that region were also examined with respect to respiratory rhythm generation. Single shock stimulation induced Pre-I neuron firing and reset the phase of the respiratory rhythm. Electrolytic lesions in the Pre-I neuron region reduced the respiratory rate.

Respiratory rhythm generator neurons in medulla of brainstem-spinal cold preparation from newborn rat

Rhythmic neuronal activity preceding C4 inspiratory activity (Pre-I neuron activity) was recorded in rostral ventrolateral (near ventral surface) medulla of brainstem-spinal cord preparation isolated from newborn rat. Vagal stimulation inhibited C4 activity but not Pre-I neuron activity. Rhythmic Pre-I neuron-like activity was still recorded in the block of rostral medulla after transection. Results suggest that Pre-I neurons generate the basic respiratory rhythm and trigger inspiratory activity.

Interactions among inspiratory neurons in dorsal and ventral respiratory groups in cat medulla.

ArticlesInteractions among inspiratory neurons in dorsal and ventral respiratory groups in cat medullaJ. L. Feldman, and D. F. SpeckJ. L. Feldman, and D. F. SpeckPublished Online:01 Feb 1983https://doi.org/10.1152/jn.1983.49.2.472MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByFree-running circadian breathing rhythms are eliminated by suprachiasmatic nucleus lesionBenton S. Purnell and Gordon F. Buchanan29 June 2020 | Journal of Applied Physiology, Vol. 129, No. 1Identification of the pre-Bötzinger complex inspiratory center in calibrated “sandwich” slices from newborn mice with fluorescent Dbx1 interneurons19 August 2014 | Physiological Reports, Vol. 2, No. 8Functional Connectivity in the Pontomedullary Respiratory NetworkLauren S. Segers, Sarah C. Nuding, Thomas E. Dick, Roger Shannon, David M. Baekey, Irene C. Solomon, Kendall F. Morris, and Bruce G. Lindsey1 October 2008 | Journal of Neurophysiology, Vol. 100, No. 4Reconfiguration of the Pontomedullary Respiratory Network: A Computational Modeling Study With Coordinated In Vivo ExperimentsI. A. Rybak, R. O'Connor, A. Ross, N. A. Shevtsova, S. C. Nuding, L. S. Segers, R. Shannon, T. E. Dick, W. L. Dunin-Barkowski, J. M. Orem, I. C. Solomon, K. F. Morris, and B. G. Lindsey1 October 2008 | Journal of Neurophysiology, Vol. 100, No. 4Medullary lateral tegmental field: control of respiratory rate and vagal lung inflation afferent influences on sympathetic nerve dischargeShaun W. Phillips, Gerard L. Gebber, and Susan M. Barman1 May 2005 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 288, No. 5Glutamatergic pathways from the Kölliker–Fuse nucleus to the phrenic nucleus in the ratBrain Research, Vol. 995, No. 1Physiological Properties of Late Inspiratory Neurons and Their Possible Involvement in Inspiratory Off-Switching in CatsAkira Haji, Mari Okazaki, Hiromi Yamazaki, and Ryuji Takeda1 February 2002 | Journal of Neurophysiology, Vol. 87, No. 2Analysis of Firing Correlations Between Sympathetic Premotor Neuron Pairs in Anesthetized CatsR. M. McAllen, D. Trevaks, and A. M. Allen1 April 2001 | Journal of Neurophysiology, Vol. 85, No. 4Functional connectivity among ventrolateral medullary respiratory neurones and responses during fictive cough in the cat1 May 2000 | The Journal of Physiology, Vol. 525, No. 1Differential Roles of Ionotropic Glutamate Receptors in Canine Medullary Inspiratory Neurons of the Ventral Respiratory GroupM. Krolo, E. A. Stuth, M. Tonkovic-Capin, Z. Dogas, F. A. Hopp, D. R. McCrimmon, and E. J. Zuperku1 July 1999 | Journal of Neurophysiology, Vol. 82, No. 1Possible mutual excitatory couplings between inspiratory neurons in caudal ventrolateral medulla of brainstem-spinal cord preparation isolated from newborn ratNeuroscience Letters, Vol. 150, No. 2Bulbospinal respiratory neurons are a source of double synapses onto phrenic motoneurons following cervical spinal cord hemisection in adult ratsBrain Research, Vol. 600, No. 1Decussation of bulbospinal respiratory axons at the level of the phrenic nuclei in adult rats: A possible substrate for the crossed phrenic phenomenonExperimental Neurology, Vol. 111, No. 1Spinal respiratory motoneuronsProgress in Neurobiology, Vol. 37, No. 2Synaptic connections between medullary respiratory neurons and considerations on the genesis of respiratory rhythmProgress in Neurobiology, Vol. 35, No. 6Effects of contralateral superior laryngeal nerve stimulation on dorsal medullary inspiratory neuronsBrain Research, Vol. 505, No. 1Dorsal medullary inspiratory neurons: effects of superior laryngeal afferent stimulationBrain Research, Vol. 491, No. 2The activity of late inspiratory cells during the behavioral inhibition of inspirationBrain Research, Vol. 458, No. 2Discharge properties of dorsal medullary inspiratory neurons in newborn pigsBrain Research, Vol. 408, No. 1-2Electrophysiological evidence for the modular organization of the reticular formation: sympathetic controlling circuitsBrain Research, Vol. 410, No. 1Discharge patterns of bulbar respiratory neurons in response to the morphinomimetic agent, fentanyl, in chloralosed dogsEuropean Journal of Pharmacology, Vol. 122, No. 3The neuronal determinants of respiratory rhythmProgress in Neurobiology, Vol. 27, No. 2Neural elements subserving pulmonary stretch receptor-mediated facilitation of phrenic motoneuronsBrain Research, Vol. 346, No. 2Responses or recurrent laryngeal motoneurons to changes of pulmonary afferent inputsRespiration Physiology, Vol. 62, No. 2Short-latency interactions among dorsomedial medullary inspiratory neurons in the catExperimental Neurology, Vol. 88, No. 3A cross-correlation study of interactions among respiratory neurons of dorsal, ventral and retrofacial groups in cat medullaBrain Research, Vol. 302, No. 1Two descending medullary inspiratory pathways to phrenic motoneuronesNeuroscience Letters, Vol. 43, No. 2-3 More from this issue > Volume 49Issue 2February 1983Pages 472-490 Copyright & PermissionsCopyright © 1983 the American Physiological Societyhttps://doi.org/10.1152/jn.1983.49.2.472PubMed6300345History Published online 1 February 1983 Published in print 1 February 1983 Metrics

Short time scale correlations between discharges of medullary respiratory neurons.

Short time scale correlations between discharges of medullary respiratory neurons.J L Feldman, D Sommer, and M I CohenJ L Feldman, D Sommer, and M I CohenPublished Online:01 May 1980https://doi.org/10.1152/jn.1980.43.5.1284MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited Byμ-Opioid receptor agonist effects on medullary respiratory neurons in the cat: evidence for involvement in certain types of ventilatory disturbancesPeter M. Lalley1 December 2003 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 285, No. 6Analysis of Firing Correlations Between Sympathetic Premotor Neuron Pairs in Anesthetized CatsR. M. McAllen, D. Trevaks, and A. M. Allen1 April 2001 | Journal of Neurophysiology, Vol. 85, No. 4Possible mutual excitatory couplings between inspiratory neurons in caudal ventrolateral medulla of brainstem-spinal cord preparation isolated from newborn ratNeuroscience Letters, Vol. 150, No. 2Synaptic connections between medullary respiratory neurons and considerations on the genesis of respiratory rhythmProgress in Neurobiology, Vol. 35, No. 6Effects of contralateral superior laryngeal nerve stimulation on dorsal medullary inspiratory neuronsBrain Research, Vol. 505, No. 1Electrophysiological evidence for the modular organization of the reticular formation: sympathetic controlling circuitsBrain Research, Vol. 410, No. 1The neuronal determinants of respiratory rhythmProgress in Neurobiology, Vol. 27, No. 2Reticular formation of the lower brainstem. A common system for cardio-respiratory and somatomotor functions. Cross-correlation analysis of discharge patterns of neighbouring neuronesJournal of the Autonomic Nervous System, Vol. 12, No. 1A cross-correlation study of interactions among respiratory neurons of dorsal, ventral and retrofacial groups in cat medullaBrain Research, Vol. 302, No. 1Postnatal synaptic development of the Nucleus Tractus Solitarius (NTS) of the ratDevelopmental Brain Research, Vol. 8, No. 2-3Short time scale interactions between brain stem neurons with sympathetic nerve-related activityBrain Research, Vol. 250, No. 1Involvement of amino acids in periodic inhibitions of bulbar respiratory neuronesBrain Research, Vol. 237, No. 2Cross-correlation of medullary dorsomedial inspiratory neurons in the catExperimental Neurology, Vol. 75, No. 3Cross correlation of medullary expiratory neurons in the catExperimental Neurology, Vol. 73, No. 2Discharge correlations between neurons in the nucleus parabrachialis medialis during sleep-waking statesBrain Research, Vol. 199, No. 2 More from this issue > Volume 43Issue 5May 1980Pages 1284-95 https://doi.org/10.1152/jn.1980.43.5.1284PubMed7373367History Published online 1 May 1980 Published in print 1 May 1980 Metrics