scholarly journals 4-Aminopyridine-sensitive outward currents in preBötzinger complex neurons influence respiratory rhythm generation in neonatal mice

2008 ◽  
Vol 586 (7) ◽  
pp. 1921-1936 ◽  
Author(s):  
John A. Hayes ◽  
Jeffrey L. Mendenhall ◽  
Benjamin R. Brush ◽  
Christopher A. Del Negro
Keyword(s):  
Respiratory Rhythm ◽  
Rhythm Generation ◽  
Neonatal Mice ◽  
Outward Currents ◽  
Respiratory Rhythm Generation ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Putting the theory into 'burstlet theory': A biophysical model of bursts and burstlets in the respiratory preBötzinger complex

2021 ◽  
Author(s):  
Ryan S Phillips ◽  
Jonathan E Rubin
Keyword(s):  
Neuronal Activity ◽  
Respiratory Rhythm ◽  
Motor Output ◽  
Biophysical Model ◽  
Extracellular Potassium ◽  
Rhythm Generation ◽  
Cationic Current ◽  
Respiratory Rhythm Generation ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

Inspiratory breathing rhythms arise from synchronized neuronal activity in a bilaterally distributed brainstem structure known as the preBötzinger complex (preBötC). In in vitro slice preparations containing the preBötC, extracellular potassium must be elevated above physiological levels (to 7-9mM) to observe regular rhythmic respiratory motor output in the hypoglossal nerve to which the preBötC projects. Reexamination of how extracellular K+ affects preBötC neuronal activity has revealed that low amplitude oscillations persist at physiological levels. These oscillatory events are sub-threshold from the standpoint of transmission to motor output and are dubbed burstlets. Burstlets arise from synchronized neural activity in a rhythmogenic neuronal subpopulation within the preBötC that in some instances may fail to recruit the larger network events, or bursts, required to generate motor output. The fraction of subthreshold preBötC oscillatory events (burstlet fraction) decreases sigmoidally with increasing extracellular potassium. These observations underlie the burstlet theory of respiratory rhythm generation. Experimental and computational studies have suggested that recruitment of the non-rhythmogenic component of the preBötC population requires intracellular Ca2+ dynamics and activation of a calcium-activated non-selective cationic current. In this computational study, we show how intracellular calcium dynamics driven by synaptically triggered Ca2+ influx as well as Ca2+ release/uptake by the endoplasmic reticulum in conjunction with a calcium-activated non-selective cationic current can explain all of the key observations underlying the burstlet theory of respiratory rhythm generation. Thus, we provide a mechanistic basis to unify the experimental findings on rhythm generation and motor output recruitment in the preBötC.

Functional Respiratory Rhythm Generating Networks in Neonatal Mice Lacking NMDAR1 Gene

1997 ◽  
Vol 78 (3) ◽  
pp. 1414-1420 ◽  
Author(s):  
G. D. Funk ◽  
S. M. Johnson ◽  
J. C. Smith ◽  
X.-W. Dong ◽  
J. Lai ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Respiratory Rhythm ◽  
Prenatal Development ◽  
Mutant Mice ◽  
Mammalian Brain ◽  
Rhythm Generation ◽  
Neonatal Mice ◽  
Respiratory Rhythm Generation ◽  
Activity Dependent

Funk, G. D., S. M. Johnson, J. C. Smith, X.-W. Dong, J. Lai, and J. L. Feldman. Functional respiratory rhythm generating networks in neonatal mice lacking NMDAR1 gene. J. Neurophysiol. 78: 1414–1420, 1997. N-methyl-d-aspartate (NMDA) receptor-mediated synaptic transmission is implicated in activity-dependent developmental reorganization in mammalian brain, including sensory systems and spinal motoneuron circuits. During normal development, synaptic interactions important in activity-dependent modification of neuronal circuits may be driven spontaneously ( Shatz 1990b ). The respiratory system exhibits substantial spontaneous activity in utero; this activity may be critical in assuring essential and appropriate breathing movements from birth. We tested the hypothesis that NMDA receptors are necessary for prenatal development of central neural circuits underlying respiratory rhythm generation by comparing the responsiveness of control mice and mutant mice lacking the NMDA receptor R1 subunit (NMDAR1) gene to glutamate receptor agonists and antagonists and comparing endogenous respiratory-related oscillations generated in vitro by brain stem-spinal cord and medullary slice preparations from control and mutant mice. In control mice, local application of NMDA and the non-NMDA receptor agonist, (R,S)-α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide (AMPA), over the pre-Bötzinger Complex, the C4 cervical motor neuron pool, and the hypoglossal motor nucleus produced profound increases in inspiratory frequency, tonic discharge on C4 ventral nerve roots, and inward currents in inspiratory hypoglossal motoneurons, respectively. Responses of mutant mice to AMPA were similar. However, mutant mice were completely unresponsive to NMDA applications. Preparations from mutant mice generated a respiratory rhythm virtually identical to control. Results demonstrate that NMDA receptors are not essential for respiratory rhythm generation or drive transmission in the neonate. More importantly, they suggest that NMDA receptors are not obligatory for the prenatal development of circuits producing respiratory rhythm.

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