scholarly journals Long term facilitation of respiratory motor output decreases with age in male rats

2001 ◽  
Vol 531 (2) ◽  
pp. 509-514 ◽  
Author(s):  
A. G. Zabka ◽  
M. Behan ◽  
G. S. Mitchell
2010 ◽  
Vol 109 (2) ◽  
pp. 279-287 ◽  
Author(s):  
M. S. Sandhu ◽  
K. Z. Lee ◽  
R. F. Fregosi ◽  
D. D. Fuller

Intermittent hypoxia (IH) can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be an important determinant of phrenic LTF. Here we test the hypothesis that acute PhrX influences immediate and long-term phrenic motor responses to hypoxia. Phrenic neurograms were recorded in anesthetized, ventilated, and vagotomized adult male rats with intact phrenic nerves or bilateral PhrX. Data were obtained before (i.e., baseline), during, and after three 5-min bouts of isocapnic hypoxia. Inspiratory burst amplitude during hypoxia (%baseline) was greater in PhrX than in phrenic nerve-intact rats ( P < 0.001). Similarly, burst amplitude 55 min after IH was greater in PhrX than in phrenic nerve-intact rats (175 ± 9 vs. 126 ± 8% baseline, P < 0.001). In separate experiments, phrenic bursting was recorded before and after PhrX in the same animal. Afferent bursting that was clearly observable in phase with lung deflation was immediately abolished by PhrX. The PhrX procedure also induced a form of facilitation as inspiratory burst amplitude was increased at 30 min post-PhrX ( P = 0.01 vs. pre-PhrX). We conclude that, after PhrX, axotomy of phrenic motoneurons and, possibly, removal of phrenic afferents result in increased phrenic motoneuron excitability and enhanced LTF following IH.


2000 ◽  
Vol 121 (2-3) ◽  
pp. 135-146 ◽  
Author(s):  
D.D Fuller ◽  
K.B Bach ◽  
T.L Baker ◽  
R Kinkead ◽  
G.S Mitchell

2016 ◽  
Vol 116 (3) ◽  
pp. 1232-1238 ◽  
Author(s):  
S. M. Turner ◽  
M. K. ElMallah ◽  
A. K. Hoyt ◽  
J. J. Greer ◽  
D. D. Fuller

Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent hypoxia (IH)]. Current synaptic models indicate enhanced effectiveness of glutamatergic synapses after IH, and we hypothesized that ampakine pretreatment would potentiate IH-induced LTF of respiratory activity. Inspiratory bursting was recorded from the hypoglossal nerve of anesthetized and mechanically ventilated mice. During baseline (BL) recording conditions, burst amplitude was stable for at least 90 min (98 ± 5% BL). Exposure to IH (3 × 1 min, 15% O2) resulted in a sustained increase in burst amplitude (218 ± 44% BL at 90 min following final bout of hypoxia). Mice given an intraperitoneal injection of ampakine CX717 (15 mg/kg) 10 min before IH showed enhanced LTF (500 ± 110% BL at 90 min). Post hoc analyses indicated that CX717 potentiated LTF only when initial baseline burst amplitude was low. We conclude that under appropriate conditions ampakine pretreatment can potentiate IH-induced respiratory LTF. These data suggest that ampakines may have therapeutic value in the context of hypoxia-based neurorehabilitation strategies, particularly in disorders with blunted respiratory motor output such as spinal cord injury.


2009 ◽  
Vol 106 (5) ◽  
pp. 1522-1528 ◽  
Author(s):  
J. M. Wenninger ◽  
E. B. Olson ◽  
C. J. Cotter ◽  
C. F. Thomas ◽  
M. Behan

It is clear that sex hormones impact ventilation. While the effects of the menstrual cycle, pregnancy, testosterone, and progesterone on resting ventilation have been well documented, effects of sex hormones on the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR) are inconclusive. In addition, in no study have systemic sex steroid hormone levels been measured. Age and sex differences in long-term facilitation in response to episodic hypoxia were found in anesthetized rats. The purpose of the present study was to assess the effects of sex and age [young, 3–4 mo; middle age, 12–13 mo; and old, >20 mo] on the HVR and the HCVR of awake rats relative to systemic hormone levels. Based on findings from long-term facilitation studies, we hypothesized that the HVR would be influenced by both sex and age. We found no age-related changes in the HVR or HCVR. However, female rats have a greater HVR than male rats at old age, and at middle age female rats have a greater HCVR than male rats. Additionally, we found no correlation between the minute ventilation/oxygen consumption and the progesterone-to-estrogen ratio during hypoxia or hypercapnia. However, changes in ventilatory responses with age were not similar between the sexes. Thus it is critical to take sex, age, estrous cycle stage, and systemic hormone levels into consideration when conducting and reporting studies on respiratory control.


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