Effects of Glycinergic Inhibition Failure on Respiratory Rhythm and Pattern Generation

To probe further the contributions of the rostral pons to eupneic respiratory rhythm and pattern, we tested the hypothesis that ibotenic acid (IA) injections in the pontine respiratory group (PRG) would disrupt eupneic respiratory rhythm and pattern in a site- and state-specific manner. In 15 goats, cannulas were bilaterally implanted into the rostral pontine tegmental nuclei (RPTN; n = 3), the lateral (LPBN; n = 4) or medial parabrachial nuclei (MPBN; n = 4), or the Kölliker-Fuse nucleus (KFN; n = 4). After recovery from surgery, 1- and 10-μl injections (1 wk apart) of IA were made bilaterally through the implanted cannulas during the day. Over the first 5 h after the injections, there were site-specific ventilatory effects, with increased ( P < 0.05) breathing frequency in RPTN-injected goats, increased ( P < 0.05) pulmonary ventilation (V̇i) in LPBN-injected goats, no effect ( P < 0.05) in MPBN-injected goats, and a biphasic V̇i response ( P < 0.05) in KFN-injected goats. This biphasic response consisted of a hyperpnea for 30 min, followed by a prolonged hypopnea and hypoventilation with marked apneas, apneusis-like breathing patterns, and/or shifts in the temporal relationships between inspiratory flow and diaphragm activity. In the awake state, 10–15 h after the 1-μl injections, the number of apneas was greater ( P < 0.05) than during other studies at night. However, there were no incidences of terminal apneas. Breathing rhythm and pattern were normal 22 h after the injections. Subsequent histological analysis revealed that for goats with cannulas implanted into the KFN, there were nearly 50% fewer neurons ( P < 0.05) in all three PRG subnuclei than in control goats. We conclude that in awake goats, 1) IA injections into the PRG have site-specific effects on breathing, and 2) the KFN contributes to eupneic respiratory pattern generation.

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Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2006.04877.x ◽

2006 ◽

Vol 24 (1) ◽

pp. 145-154 ◽

Cited By ~ 16

Author(s):

Ming-Gao Zhao ◽

Swen Hülsmann ◽

Stefan M. Winter ◽

Mathias Dutschmann ◽

Diethelm W. Richter

Keyword(s):

Respiratory Rhythm ◽

Potassium Currents ◽

Rhythm Generation ◽

Respiratory Rhythm Generation ◽

Glycinergic Inhibition

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Fast and Slow Locomotor Burst Generation in the Hemispinal Cord of the Lamprey

Journal of Neurophysiology ◽

10.1152/jn.01100.2002 ◽

2003 ◽

Vol 89 (6) ◽

pp. 2931-2942 ◽

Cited By ~ 83

Author(s):

Lorenzo Cangiano ◽

Sten Grillner

Keyword(s):

Spinal Cord ◽

Reciprocal Inhibition ◽

Pattern Generation ◽

Burst Activity ◽

Burst Frequency ◽

Glutamatergic Neurons ◽

Voltage Dependent ◽

Burst Pattern ◽

Glycinergic Inhibition ◽

Electrical Stimuli

A fundamental question in vertebrate locomotion is whether distinct spinal networks exist that are capable of generating rhythmic output for each group of muscle synergists. In many vertebrates including the lamprey, it has been claimed that burst activity depends on reciprocal inhibition between antagonists. This question was addressed in the isolated lamprey spinal cord in which the left and right sides of each myotome display rhythmic alternating activity. We sectioned the spinal cord along the midline and tested whether rhythmic motor activity could be induced in the hemicord with bath-applied d-glutamate or N-methyl-d-aspartate (NMDA) as in the intact spinal cord or by brief trains of electrical stimuli. Fast rhythmic bursting (2–12 Hz), coordinated across ventral roots, was observed with all three methods. Furthermore, to diminish gradually the crossed glycinergic inhibition, a progressive surgical lesioning of axons crossing the midline was implemented. This resulted in a gradual increase in burst frequency, linking firmly the fast hemicord rhythm [6.6 ± 1.7 (SD) Hz] to fictive swimming in the intact cord (2.4 ± 0.7 Hz). Ipsilateral glycinergic inhibition was not required for the hemicord burst pattern generation, suggesting that an interaction between excitatory glutamatergic neurons suffices to produce the unilateral burst pattern. In NMDA, burst activity at a much lower rate (0.1–0.4 Hz) was also encountered, which required the voltage-dependent properties of NMDA receptors in contrast to the fast rhythm. Swimming is thus produced by pairs of unilateral burst generating networks with reciprocal inhibitory connections that not only ensure left/right alternation but also downregulate frequency.

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Subtype Composition and Responses of Respiratory Neurons in the Pre-Bötzinger Region to Pulmonary Afferent Inputs in Dogs

Journal of Neurophysiology ◽

10.1152/jn.01206.2003 ◽

2005 ◽

Vol 93 (5) ◽

pp. 2674-2687 ◽

Cited By ~ 25

Author(s):

M. Krolo ◽

V. Tonkovic-Capin ◽

A. G. Stucke ◽

E. A. Stuth ◽

F. A. Hopp ◽

...

Keyword(s):

Motor Pattern ◽

Respiratory Rhythm ◽

Pattern Generation ◽

Respiratory Neurons ◽

Neural Responses ◽

Neuronal Responses ◽

Phase Duration ◽

Homocysteic Acid ◽

Spike Triggered Averaging ◽

Afferent Inputs

The brain stem pre-Bötzinger complex (pre-BC) plays an important role in respiratory rhythm generation. However, it is not clear what function each subpopulation of neurons in the pre-BC serves. The purpose of the present studies was to identify neuronal subpopulations of the canine pre-BC and to characterize the neuronal responses of subpopulations to experimentally imposed changes in inspiratory (I) and expiratory (E) phase durations. Lung inflations and electrical stimulation of the cervical vagus nerve were used to produce changes in respiratory phase timing via the Hering-Breuer reflex. Multibarrel micropipettes were used to record neuronal activity and for pressure microejection in decerebrate, paralyzed, ventilated dogs. The pre-BC region was functionally identified by eliciting tachypneic phrenic neural responses to localized microejections of dl-homocysteic acid. Antidromic stimulation and spike-triggered averaging techniques were used to identify bulbospinal and cranial motoneurons, respectively. The results indicate that the canine pre-BC region consists of a heterogeneous mixture of propriobulbar I and E neuron subpopulations. The neuronal responses to ipsi-, contra-, and bilateral pulmonary afferent inputs indicated that I and E neurons with decrementing patterns were the only neurons with responses consistently related to phase duration. Late-I neurons were excited, but most other types of I neurons were inhibited or unresponsive. E neurons with augmenting or parabolic discharge patters were inhibited by ipsilateral inputs but excited by contra- and bilateral inputs. Late-E neurons were more frequently encountered and were inhibited by ipsi- and bilateral inputs, but excited by contralateral inputs. The results suggest that only a limited number of neuron subpopulations may be involved in rhythmogenesis, whereas many neuron types may be involved in motor pattern generation.

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