Serotonergic modulation of respiratory motor output during tadpole development

2002 ◽  
Vol 93 (3) ◽  
pp. 936-946 ◽  
Author(s):  
Richard Kinkead ◽  
Olivier Belzile ◽  
Roumiana Gulemetova
Keyword(s):  
Brain Stem ◽  
Lung Ventilation ◽  
Receptor Activation ◽  
Motor Output ◽  
Burst Frequency ◽  
Bath Application ◽  
Age Dependent ◽  
Dose Dependent ◽  
Serotonergic Modulation

To test the hypothesis that serotonin (5-hydroxytryptamine; 5-HT)-receptor activation elicits age-dependent changes in respiratory motor output, we compared the effects of 5-HT bath application (5-HT concentration = 0.5–25 μM) onto in vitro brain stem preparations from pre- and postmetamorphic bullfrog tadpoles. Recording of motor output related to gill and lung ventilation showed that 5-HT elicits a dose-dependent depression of gill burst frequency in both groups. In contrast, the lung burst frequency response was stage dependent; an increase in lung burst frequency at low 5-HT concentration (≤0.5 μM) was observed only in the postmetamorphic group. Higher 5-HT concentrations decreased lung burst frequency in all preparations. Gill burst frequency attenuation is mediated (at least in part) by 5-HT1A-receptor activation in an age-dependent fashion. We conclude that serotonergic modulation of respiratory motor output 1) changes during tadpole development and 2) is distinct for gill and lung ventilation.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

scholarly journals Muscarinic Receptor Activation Elicits Sustained, Recurring Depolarizations in Reticulospinal Neurons

2007 ◽  
Vol 97 (5) ◽  
pp. 3181-3192 ◽  
Author(s):  
R. W. Smetana ◽  
S. Alford ◽  
R. Dubuc
Keyword(s):  
Brain Stem ◽  
Muscarinic Receptor ◽  
Central Pattern Generators ◽  
Receptor Activation ◽  
Motor Output ◽  
Reticular Nucleus ◽  
Muscarinic Agonists ◽  
Bath Application ◽  
Descending Input ◽  
Pattern Generators

In lampreys, brain stem reticulospinal (RS) neurons constitute the main descending input to the spinal cord and activate the spinal locomotor central pattern generators. Cholinergic nicotinic inputs activate RS neurons, and consequently, induce locomotion. Cholinergic muscarinic agonists also induce locomotion when applied to the brain stem of birds. This study examined whether bath applications of muscarinic agonists could activate RS neurons and initiate motor output in lampreys. Bath applications of 25 μM muscarine elicited sustained, recurring depolarizations (mean duration of 5.0 ± 0.5 s recurring with a mean period of 55.5 ± 10.3 s) in intracellularly recorded rhombencephalic RS neurons. Calcium imaging experiments revealed that muscarine induced oscillations in calcium levels that occurred synchronously within the RS neuron population. Bath application of TTX abolished the muscarine effect, suggesting the sustained depolarizations in RS neurons are driven by other neurons. A series of lesion experiments suggested the caudal half of the rhombencephalon was necessary. Microinjections of muscarine (75 μM) or the muscarinic receptor (mAchR) antagonist atropine (1 mM) lateral to the rostral pole of the posterior rhombencephalic reticular nucleus induced or prevented, respectively, the muscarinic RS neuron response. Cells immunoreactive for muscarinic receptors were found in this region and could mediate this response. Bath application of glutamatergic antagonists (6-cyano-7-nitroquinoxaline-2,3-dione/d-2-amino-5-phosphonovaleric acid) abolished the muscarine effect, suggesting that glutamatergic transmission is needed for the effect. Ventral root recordings showed spinal motor output coincides with RS neuron sustained depolarizations. We propose that unilateral mAchR activation on specific cells in the caudal rhombencephalon activates a circuit that generates synchronous sustained, recurring depolarizations in bilateral populations of RS neurons.

scholarly journals Fictive Rhythmic Motor Patterns Induced by NMDA in an In Vitro Brain Stem–Spinal Cord Preparation From an Adult Urodele

1999 ◽  
Vol 82 (2) ◽  
pp. 1074-1077 ◽  
Author(s):  
Isabelle Delvolvé ◽  
Pascal Branchereau ◽  
Réjean Dubuc ◽  
Jean-Marie Cabelguen
Keyword(s):  
Spinal Cord ◽  
Brain Stem ◽  
Rhythm Generation ◽  
Motor Patterns ◽  
Rhythmic Motor ◽  
Bath Application ◽  
The Neural Networks ◽  
Ventral Roots ◽  
Pleurodeles Waltl

An in vitro brain stem–spinal cord preparation from an adult urodele ( Pleurodeles waltl) was developed in which two fictive rhythmic motor patterns were evoked by bath application of N-methyl-d-aspartate (NMDA; 2.5–10 μM) with d-serine (10 μM). Both motor patterns displayed left-right alternation. The first pattern was characterized by cycle periods ranging between 2.4 and 9.0 s (4.9 ± 1.2 s, mean ± SD) and a rostrocaudal propagation of the activity in consecutive ventral roots. The second pattern displayed longer cycle periods (8.1–28.3 s; 14.2 ± 3.6 s) with a caudorostral propagation. The two patterns were inducible after a spinal transection at the first segment. Preliminary experiments on small pieces of spinal cord further suggested that the ability for rhythm generation is distributed along the spinal cord of this preparation. This study shows that the in vitro brain stem–spinal cord preparation from Pleurodeles waltl may be a useful model to study the mechanisms underlying the different axial motor patterns and the flexibility of the neural networks involved.

Vagal input enhances responsiveness of respiratory discharge to central changes in pH/CO2 in bullfrogs

1994 ◽  
Vol 77 (4) ◽  
pp. 2048-2051 ◽  
Author(s):  
R. Kinkead ◽  
W. G. Filmyer ◽  
G. S. Mitchell ◽  
W. K. Milsom
Keyword(s):  
Breathing Pattern ◽  
Intrinsic Property ◽  
Afferent Input ◽  
Motor Output ◽  
Burst Frequency ◽  
Central Chemosensitivity ◽  
Temporal Relationships ◽  
The Central Nervous System ◽  
Motor Nerves

This study investigated the interaction between vagal afferent input and central chemosensitivity in modulating the respiratory motor output of in vitro brain stem-spinal cord preparations from adult bullfrogs. With this preparation, the spatiotemporal distribution of respiratory-related motor output emulated that of intact bullfrogs; that is, the fictive breathing pattern was mostly episodic. Recordings from cranial motor nerves (V and X) showed that, without peripheral feedback, increasing the PCO2 of the mock cerebrospinal fluid (thereby reducing pH from 8.3 to 7.7) caused a modest increase in respiration-related burst frequency. When the pulmonary branch of a vagus nerve was stimulated phasically (2 V, 20 Hz, 0.2 ms) during each fictive breath to simulate afferent pulmonary stretch receptor feedback 1) the responsiveness of the preparation to the same changes in pH was augmented nearly threefold and 2) the breathing pattern remained episodic. It appears, therefore, that episodic breathing is an intrinsic property of the central nervous system in bullfrogs. It is concluded that there is a strong interaction between vagal feedback and central chemodetection in controlling the temporal relationships that characterize this episodic breathing pattern.

Modulation of the biological activity of thyrotrophin by anti-human thyrotrophin monoclonal antibodies

1990 ◽  
Vol 126 (2) ◽  
pp. 333-340 ◽  
Author(s):  
S. R. Page ◽  
A. H. Taylor ◽  
W. Driscoll ◽  
M. Baines ◽  
R. Thorpe ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Biological Activity ◽  
Monoclonal Antibodies ◽  
Cyclic Amp ◽  
Receptor Activation ◽  
Camp Production ◽  
Dose Dependent ◽  
Bovine Tsh

ABSTRACT The mechanism by which monoclonal antibodies enhance the biological activity of a number of hormones is poorly understood. One such antibody (GC73), which binds to human but not bovine TSH, enhances the bioactivity of human TSH in vivo. We have investigated whether GC73 enhancement of TSH bioactivity involves potentiation of hormone-receptor activation assessed by the cyclic AMP (cAMP) responses of both primary human thyrocyte cultures and a TSH-responsive human thyrocyte cell line (SGHTL-45). GC73 had no effect on basal cAMP production. In contrast to its enhancement of the bioactivity of human TSH in vivo, it markedly inhibited the cAMP response to 1 and 10 mU human TSH/ml in primary thyrocytes. This effect was dose-dependent with neutralization of the bioactivity of TSH occurring at 2 mg GC73/ml. GC73 had no effect on the bioactivity of bovine TSH. In contrast, a second anti-TSH monoclonal antibody (TC12), which binds to both human and bovine TSH, inhibited the bioactivity of both species of TSH. Similar results were obtained using SGHTL-45 cells, although the peak concentrations of cAMP were lower. We conclude that binding of GC73 to human TSH resulted in inhibition rather than enhancement of the in-vitro biological activity of human TSH. We suggest that GC73 enhancement of human TSH bioactivity seen in vivo does not result from a mechanism involving potentiation of receptor activation by human TSH. Journal of Endocrinology (1990) 126, 333–340

scholarly journals Organotypic slice cultures containing the preBötzinger complex generate respiratory-like rhythms

2016 ◽  
Vol 115 (2) ◽  
pp. 1063-1070 ◽  
Author(s):  
Wiktor S. Phillips ◽  
Mikkel Herly ◽  
Christopher A. Del Negro ◽  
Jens C. Rekling
Keyword(s):  
Brain Stem ◽  
Drug Exposure ◽  
Fluorescent Dyes ◽  
Calcium Oscillations ◽  
Oscillatory Activity ◽  
Slice Culture ◽  
Burst Frequency ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

Study of acute brain stem slice preparations in vitro has advanced our understanding of the cellular and synaptic mechanisms of respiratory rhythm generation, but their inherent limitations preclude long-term manipulation and recording experiments. In the current study, we have developed an organotypic slice culture preparation containing the preBötzinger complex (preBötC), the core inspiratory rhythm generator of the ventrolateral brain stem. We measured bilateral synchronous network oscillations, using calcium-sensitive fluorescent dyes, in both ventrolateral (presumably the preBötC) and dorsomedial regions of slice cultures at 7–43 days in vitro. These calcium oscillations appear to be driven by periodic bursts of inspiratory neuronal activity, because whole cell recordings from ventrolateral neurons in culture revealed inspiratory-like drive potentials, and no oscillatory activity was detected from glial fibrillary associated protein-expressing astrocytes in cultures. Acute slices showed a burst frequency of 10.9 ± 4.2 bursts/min, which was not different from that of brain stem slice cultures (13.7 ± 10.6 bursts/min). However, slice cocultures that include two cerebellar explants placed along the dorsolateral border of the brainstem displayed up to 193% faster burst frequency (22.4 ± 8.3 bursts/min) and higher signal amplitude (340%) compared with acute slices. We conclude that preBötC-containing slice cultures retain inspiratory-like rhythmic function and therefore may facilitate lines of experimentation that involve extended incubation (e.g., genetic transfection or chronic drug exposure) while simultaneously being amenable to imaging and electrophysiology at cellular, synaptic, and network levels.

Nucleus raphé obscurus modulates hypoglossal output of neonatal rat in vitro transverse brain stem slices

2001 ◽  
Vol 90 (1) ◽  
pp. 269-279 ◽  
Author(s):  
John H. Peever ◽  
Aleksandar Necakov ◽  
James Duffin
Keyword(s):  
Brain Stem ◽  
Control Region ◽  
Motor Output ◽  
Discharge Frequency ◽  
Burst Discharge ◽  
Burst Amplitude ◽  
Chemical Ablation ◽  
Brain Stem Slices ◽  
Stem Slices

Nucleus raphéobscurus (NRo) modulates hypoglossal (XII) nerve motor output in the in vitro transverse brain stem slice of neonatal rats (1–5 days old); chemical ablation of NRo and its focal CO2 acidification modulated the bursting rhythm of XII nerves. We microinjected a 4.5 mM solution of kainic acid into the NRo to disrupt cellular activity and observed that XII nerve activity was temporarily abolished ( n = 10). We also microinjected CO2-acidified (pH = 6.00 ± 0.01) artificial cerebrospinal fluid (aCSF) into the NRo ( n = 6), the pre-Bötzinger complex (PBC) ( n = 6), as well as a control region in the lateral tegmental field equidistant to NRo, PBC, and the XII motor nuclei ( n = 12). CO2acidification of the control region had no effect on XII motor output. CO2 acidification of the NRo significantly ( P < 0.05) increased the burst discharge frequency of XII nerves by 77%; integrated burst amplitude and burst duration increased by 64% and 52%, respectively. CO2 acidification of the PBC significantly ( P < 0.05) increased the burst discharge frequency of XII nerves by 65%, but neither integrated burst amplitude nor burst duration changed. These results demonstrate that chemical ablation of the NRo can abolish XII nerve bursting rhythm and that stimulation of the NRo with CO2-acidified aCSF can excite XII nerve bursting activity. From these observations, we conclude that, in transverse brain stem slices, the NRo contains pH/CO2-sensitive cells that modulate XII motor output.

In vitro recordings from area postrema neurons demonstrate responsiveness to adrenomedullin

1996 ◽  
Vol 270 (4) ◽  
pp. R920-R925 ◽  
Author(s):  
M. A. Allen ◽  
A. V. Ferguson
Keyword(s):  
Fluid Balance ◽  
Area Postrema ◽  
Brain Slices ◽  
Amino Acid Peptide ◽  
Artificial Cerebrospinal Fluid ◽  
Bath Application ◽  
Single Unit Recordings ◽  
Body Fluid Balance ◽  
Dose Dependent

Adrenomedullin (ADM) is a recently discovered 52-amino acid peptide that exerts potent vasodilatory effects in the periphery and influences the control of body fluid balance when injected centrally. In this study extracellular single-unit recordings were obtained from 94 AP neurons in rat brain slices. Bath application of ADM (10(-7) M) excited 47% (32 of 68) of cells tested, and these effects were found to be dose dependent from 10(-7) to 10(-9) M. Excitation was maintained during synaptic blockade in a low-Ca2+ artificial cerebrospinal fluid solution, demonstrating direct actions of ADM on these neurons. The remaining cells were either unaffected (n = 25) or inhibited (n = 11) by ADM. ADM (10(-7) M) also influenced the spontaneous activity of 9 (7 inhibited, 2 excited) of 16 neurons located in the nucleus tractus solitarii (NTS). However, these effects could be eliminated during synaptic blockade, suggesting indirect actions of the peptide on NTS neurons. These data demonstrate that a specific population of CNS neurons within the AP are directly influenced by ADM and suggest that ADM may exert its effects on the central control of fluid balance through direct actions at this circumventricular organ.

Excitatory and inhibitory effects of tricaine (MS-222) on fictive breathing in isolated bullfrog brain stem

2003 ◽  
Vol 284 (2) ◽  
pp. R405-R412 ◽  
Author(s):  
Michael S. Hedrick ◽  
Rachel E. Winmill
Keyword(s):  
Brain Stem ◽  
Rana Catesbeiana ◽  
Motor Output ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Artificial Cerebrospinal Fluid ◽  
Channel Blocking ◽  
The Central Nervous System ◽  
Excitatory Neurotransmission

This study examined the direct effects of tricaine methanesulfonate (MS-222), a sodium-channel blocking local anesthetic, on respiratory motor output using an in vitro brain stem preparation of adult North American bullfrogs ( Rana catesbeiana). Bullfrogs were anesthetized with halothane, and the brain stem was removed and superfused with artificial cerebrospinal fluid containing MS-222 at concentrations ranging from 0.1 to 1,000 μM. At the lowest concentration of MS-222, respiratory frequency ( f R) increased significantly ( P < 0.05), but at higher concentrations, f R progressively decreased and was abolished in all preparations at 1,000 μM ( P < 0.01). Respiratory burst amplitude and burst duration were not affected by MS-222. The frequency of nonrespiratory neural activity did not significantly change with the addition of MS-222 below 1,000 μM. These data indicate that MS-222 has a significant, direct effect on respiratory motor output from the central nervous system, producing both excitation and inhibition of fictive breathing. The results are consistent with other studies demonstrating that low concentrations of anesthetics generally cause excitation followed by depression at higher concentrations. Although the mechanisms underlying the excitatory effects of MS-222 in this study are unclear, they may include increased excitatory neurotransmission and/or disinhibition of inputs to the respiratory central pattern generator.

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