CO2-induced c-fos expression in medullary neurons during early development

Belegu, R; Hadziefendic, Selma; Dreshaj, Ismail A.; Haxhiu, Musa A.; Martin, Richard J.

doi:10.1016/s0034-5687(99)00046-8

Cited by 34 publications

(33 citation statements)

References 28 publications

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“…The number of CO 2 -sensitive cells did increase in the lateral reticular nucleus as animals grew older. The c-Fos labeling was less in the midline raphé than Belegu et al (1999) described, but in neither study were CO 2 -sensitive neurons identified in the locus coeruleus (Wickström et al, 2002).…”

Section: Developmental Changes In Neurons From Various Chemosensitivecontrasting

confidence: 57%

“…Based on these findings, both the number of chemosensitive neurons and the magnitude of their response to hypercapnia increase during early development in the medullary raphé. These findings are at odds with studies described below in which Fos labeling was used to estimate the number of CO 2 -sensitive neurons (Belegu et al, 1999).…”

Section: Developmental Changes In Neurons From Various Chemosensitivementioning

confidence: 63%

“…Thus, like LC neurons, chemosensitive NTS neurons are fully developed at birth and do not appear to change their properties with development. Belegu et al (1999) and Wickström et al (2002) used a different, non-electrophysiological approach to study the development of chemosensitivity in different brainstem regions by using Fos labeling to identify cells activated by hypercapnia. This method is not quantitative; it identifies the number of cells that are activated by CO 2 , but indicates nothing about the relative sensitivity to CO 2 among the Fos-positive cells.…”

Section: Developmental Changes In Neurons From Various Chemosensitivementioning

confidence: 99%

“…Furthermore, Fos positivity may reflect the activation of intrinsically CO 2 -sensitive neurons, but it may also reflect synaptically driven activity from other sites, such as the carotid body. Belegu et al (1999) studied rat pups at P5, P15 and P40 after exposure to 10% inhaled CO 2 for 1 h. They found increased numbers of Fos (+) cells after hypercapnic stimulation in the NTS, along the ventral surface of the brainstem, the RTN and the midline raphé. The number of stimulated Fos(+) neurons was stable across ages P5-P40 except in the raphé nuclei where the number of CO 2 -stimulated neurons declined as animals matured-the opposite of the effect described by Wang and Richerson (1999).…”

Section: Developmental Changes In Neurons From Various Chemosensitivementioning

confidence: 99%

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Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Putnam

Conrad

Gdovin

et al. 2005

Respiratory Physiology & Neurobiology

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The ventilatory response to CO 2 changes as a function of neonatal development. In rats, a ventilatory response to CO 2 is present in the first 5 days of life, but this ventilatory response to CO 2 wanes and reaches its lowest point around postnatal day 8. Subsequently, the ventilatory response to CO 2 rises towards adult levels. Similar patterns in the ventilatory response to CO 2 are seen in some other species, although some animals do not exhibit all of these phases. Different developmental patterns of the ventilatory response to CO 2 may be related to the state of development of the animal at birth. The triphasic pattern of responsiveness (early decline, a nadir, and subsequent achievement of adult levels of responsiveness) may arise from the development of several processes, including central neural mechanisms, gas exchange, the neuromuscular junction, respiratory muscles and respiratory mechanics. We only discuss central neural mechanisms here, including altered CO 2 sensitivity of neurons among the various sites of central CO 2 chemosensitivity, changes in astrocytic function during development, the maturation of electrical and chemical synaptic mechanisms (both inhibitory and excitatory mechanisms) or changes in the integration of chemosensory information originating from peripheral and multiple central CO 2 chemosensory sites. Among these central processes, the maturation of synaptic mechanisms seems most important and the relative maturation of synaptic processes may also determine how plastic the response to CO 2 is at any particular age.

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Section: Developmental Changes In Neurons From Various Chemosensitivecontrasting

confidence: 57%

Section: Developmental Changes In Neurons From Various Chemosensitivementioning

confidence: 63%

Section: Developmental Changes In Neurons From Various Chemosensitivementioning

confidence: 99%

Section: Developmental Changes In Neurons From Various Chemosensitivementioning

confidence: 99%

See 2 more Smart Citations

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Putnam

Conrad

Gdovin

et al. 2005

Respiratory Physiology & Neurobiology

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“…Alternatively, the possibility should be considered that Fos expression might be partly related to side effects of hypoventilation, such as hypoxia and/or hypercapnia, and/or related cardiovascular adjustments. Nevertheless, the distribution of Fos expression evoked by these stimuli was much more extensive than after DOI injection (15,23).…”

Section: Discussionmentioning

confidence: 95%

5-HT2A/2C Receptor–Mediated Hypopnea in the Newborn Rat: Relationship to Fos Immunoreactivity

Cayetanot¹,

Gros²,

Larnicol³

2001

Pediatr Res

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Previous data derived from anesthetized, decerebrate, or in vitro preparations suggested that 5-HT 2 receptor activation might be responsible for respiratory dysfunction. Such a mechanism has not yet been documented in the intact animal, but might be of clinical relevance to the apneic spells of the premature infant. In the present investigation on conscious newborn rats we analyzed the respiratory response to the activation of 5-HT 2A/2C receptors by the agonist 1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and we delineated central structures possibly involved in this response, using Fos expression as a marker of neuronal activation. We demonstrated that intraperitoneal injection of 5 mg/kg DOI produced a long-lasting decrease in respiratory frequency and tidal volume, which could be blocked by the antagonist ritanserin. Fos immunohistochemistry suggested that the rostral ventrolateral medulla and the lateral paragigantocellular nucleus might have a key role in the respiratory response to 5-HT 2 receptor activation. In addition, double immunostaining for Fos and tyrosine hydroxylase suggested that the contribution of catecholaminergic neurons to this response might be modest and indirect. Serotonin (5-hydroxytryptamine; 5-HT) acting at 5-HT 2 receptors has been involved in the neuromodulation of a broad spectrum of functions ranging from mental processing to autonomic regulation (1). 5-HT also interferes with breathing control, via central and peripheral 5-HT 2 receptors, and variable responses have been reported. In vitro studies on brain stem-spinal cord preparations isolated from the newborn rat indicated that central 5-HT 2A receptor mechanisms may exert facilitating influences on respiration, by activating spinal respiratory motoneurons (2) and increasing the frequency of rhythmic respiratory discharge (3). In contrast, in adult anesthetized rats, the activation of 5-HT 2 receptors located at the periphery has been involved in decreases in phrenic nerve activity and lung compliance observed during apnea induced by 5-HT (4). In decerebrate newborn rats, the application of 5-HT 2A/2C receptor agonists to the floor of the fourth ventricle elicited a bradypnea (5), reminiscent of the decrease in frequency of respiratory-like activity that followed bath application of 5-HT 2C receptor agonists to in vitro preparations (3). Furthermore, the finding that 5-HT 2A/2C receptor agonists inhibit hypoglossal inspiratory activity in isolated brain stemspinal cord preparations led to the hypothesis that 5-HT 2 receptors may be involved in the genesis of obstructive apneas in newborns with increased 5-HT biosynthesis (2, 6). Nevertheless, the depressant influence of 5-HT 2 receptor activation on hypoglossal activity has not been confirmed on medullary rhythmic slice (7). Altogether, those findings suggest that 5-HT 2 receptor mechanisms might influence the network devoted to respiratory control at multiple levels and that the response to 5-HT 2 receptor activation in the intact animal may not be definitely deduced...

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Fos expression in otolith‐related brainstem neurons of postnatal rats following off‐vertical axis rotation

Lai

Tse

Shum

et al. 2004

J of Comparative Neurology

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To determine the critical time of responsiveness of developing otolith organ-related brainstem neurons and their distribution, Fos protein expression in response to off-vertical axis rotations (OVAR) was mapped in conscious Sprague Dawley rats from P5 to adulthood. OVAR was used to activate sequentially all utricular hair cells per 360 degrees revolution. We detected the coding of horizontal head positions in otolith organ-related neurons within the vestibular nucleus as early as P7. In the vestibular nuclear complex and its subgroups, the density of Fos-immunoreactive (Fos-ir) neurons increased steadily with age and reached the adult level by P21. In both labyrinthectomized rats subjected to OVAR and normal rats kept stationary, labeled neurons were found sporadically in the aforementioned brain regions in each age group, confirming that Fos labeling observed in neurons of normal experimental rats subjected to OVAR was due to otolith organ stimulation. Whereas OVAR-induced Fos-ir neurons were also first observed in vestibular-related brain areas, such as the prepositus hypoglossal nucleus, gigantocellular reticular nucleus, and locus coeruleus, of normal experimental rats at P7, those in the inferior olive were observed only from P14 onward. This indicates the unique maturation time of inferior olivary neurons in gravity-related spatial coding. In general, age-dependent increase in OVAR-induced Fos-ir neurons was observed in brain areas that received otolith inputs. The locus coeruleus was exceptional in that prominent OVAR-induced Fos-ir neuronal number did not change with maturation, and this was well above the low but significant number of Fos-ir neurons in control preparations. Taken together, our results suggest that neuronal subpopulations within the developing network of the horizontal otolith system provide an anatomical basis for the postnatal development of otolith organ-related sensorimotor functions. J. Comp. Neurol. 470:282-296, 2004.

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CO2-induced c-fos expression in medullary neurons during early development

Cited by 34 publications

References 28 publications

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

5-HT2A/2C Receptor–Mediated Hypopnea in the Newborn Rat: Relationship to Fos Immunoreactivity

Fos expression in otolith‐related brainstem neurons of postnatal rats following off‐vertical axis rotation

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