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Eugene Nattie

Publications and source records attributed to Eugene Nattie.

11 recordsLinked to original sources
PubMed2006

Neurokinin-1 receptor-expressing neurons in the ventral medulla are essential for normal central and peripheral chemoreception in the conscious rat.

Neurokinin-1 receptor immunoreactive (NK1R-ir) neurons and processes are widely distributed within the medulla, prominently at central chemoreceptor sites. Focal lesions of NK1R-ir neurons in the medullary raphe or the retrotrapezoid nucleus partially reduced the CO(2) response in conscious rats. We ask if NK1R-ir cells and processes over a wide region of the ventral medulla are essential for central and peripheral chemoreception by cisterna magna injection of SSP-SAP, a high-affinity version of substance P-saporin. After 22 days, NK1R-ir cell loss was -79% in the retrotrapezoid nucleus and -65% in the A5 region, which lie close to the ventral surface, and -38% in the medullary raphe and -49% in the pre-Bötzinger complex/rostral ventral respiratory group, which lie deeper. Dorsal chemoreceptor sites, the caudal nucleus tractus solitarius and the A6 region, were unaffected. At 8 and 22 days, these lesions produced 1) hypoventilation during air breathing in wakefulness ( approximately 8%) and in non-rapid eye movement (NREM) ( approximately 9%) and rapid eye movement ( approximately 14%) sleep, as measured over a 4-h period; 2) a substantially reduced ventilatory response to 7% CO(2) by 61% in wakefulness and 46-57% in NREM sleep; and 3) a decreased ventilatory response to 12% O(2) by 40% in wakefulness and 35% in NREM sleep at 8 days, with partial recovery by 22 days. NK1R-ir neurons in the ventral medulla are essential for normal central chemoreception, provide a drive to breathe, and modulate the peripheral chemoreceptor responses. These effects are not state dependent.

Animals↗
PubMed2006

Simultaneous inhibition of caudal medullary raphe and retrotrapezoid nucleus decreases breathing and the CO2 response in conscious rats.

The medullary raphe (MR) and the retrotrapezoid nucleus (RTN) in the ventral medulla are two of many central chemoreceptor sites. We examine their combined function in conscious rats by focal inhibition using microdialysis. Inhibition of RTN neurons with the GABA(A) receptor agonist muscimol, with simultaneous dialysis of artificial cerebrospinal fluid (ACSF) in or near to the caudal MR, causes hypoventilation (decrease in the ratio of minute ventilation to oxygen consumption, V(E)/V(O2)) and reduces the ventilatory response to 7% CO(2) by 24%. Inhibition of caudal MR serotonergic neurons with the 5-HT(1A) receptor agonist (R)-(+)-8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), with simultaneous dialysis of ACSF in or near to the RTN, causes hypoventilation but has no significant effect on the CO(2) response. Inhibition of both the RTN and the caudal MR simultaneously produces enhanced hypoventilation and a 51% decrease in the CO(2) response. The effects of treatment on the CO(2) response are similar in wakefulness and in non-rapid eye movement sleep. Comparison of the effect of 8-OH-DPAT microdialysed into a more rostral portion of the MR, where the CO(2) response is reduced by 22%, demonstrates heterogeneity within the MR of the function of serotonergic neurons in breathing. We conclude that serotonergic neurons within the caudal MR provide a non-CO(2)-dependent tonic drive to breathe and potentiate the effects of RTN neurons that contribute to a resting chemical 'drive to breathe' as well as the response to added CO(2). These effects of caudal MR serotonergic neurons could be at a chemoreceptor site, e.g. the RTN, or at 'downstream' sites involved in rhythm and pattern generation.

Animals↗
PubMed2006

Central chemoreception 2005: a brief review.

This brief review will place recent findings on specific neurons and receptors identified as putative central chemoreceptors, namely glutamatergic and serotonergic neurons and purogenic receptors, into the context of our working hypothesis that central chemoreception is a distributed property.

Anesthesia↗
PubMed2005

Catecholamine neurones in rats modulate sleep, breathing, central chemoreception and breathing variability.

Brainstem catecholamine (CA) neurones have wide projections and an arousal-state-dependent activity pattern. They are thought to modulate the processing of sensory information and also participate in the control of breathing. Mice with lethal genetic defects that include CA neurones have abnormal respiratory control at birth. Also the A6 region (locus coeruleus), which contains CA neurones sensitive to CO(2) in vitro, is one of many putative central chemoreceptor sites. We studied the role of CA neurones in the control of breathing during sleep and wakefulness by specifically lesioning them with antidopamine beta-hydroxylase-saporin (DBH-SAP) injected via the 4th ventricle. After 3 weeks there was a 73-84% loss of A5, A6 and A7 tyrosine hydroxylase (TH) immunoreactive (ir) neurones along with 56-60% loss of C1 and C2 phenyl ethanolamine-N-methyltransferase (PNMT)-ir neurones. Over the 3 weeks, breathing frequency decreased significantly during air and 3 or 7% CO(2) breathing in both wakefulness and non-REM (NREM) sleep. The rats spent significantly less time awake and more time in NREM sleep. REM sleep time was unaffected. The ventilatory response to 7% CO(2) was reduced significantly in wakefulness at 7, 14 and 21 days (-28%) and in NREM sleep at 14 and 21 days (-26%). Breathing variability increased in REM sleep but not in wakefulness or NREM sleep. We conclude that CA neurones (1) promote wakefulness, (2) participate in central respiratory chemoreception, (3) stimulate breathing frequency, and (4) minimize breathing variability in REM sleep.

Animals↗
PubMed2002

CO2 dialysis in one chemoreceptor site, the RTN: stimulus intensity and sensitivity in the awake rat.

We stimulate single central chemoreceptor sites in the unanesthetized rat by focal microdialysis of artificial cerebrospinal fluid (aCSF) equilibrated with 25% CO(2). Here, in the retrotrapezoid nucleus (RTN) we measured the focal stimulus intensity with a pH electrode adjacent to the dialysis probe. During 25% CO(2) dialysis, RTN pH decreased by 0.069 (0.013, SEM) pH units (N=5), 44% of the change observed during 7% CO(2) breathing, -0.157 (0.019) pH units (N=4). During 7% CO(2) breathing, Pa(CO(2)) increased by 15 Torr (N=5). We calculate the deltaPa(CO(2)) that would produce a deltapH at the RTN approximately like that observed during 25% CO(2) dialysis as 44% of 15 Torr, or 6.6 Torr deltaPa(CO(2)). Using ventilatory response data from our lab, we estimate overall chemoreceptor sensitivity as 13% deltaVE/Torr deltaPa(CO(2)) and RTN sensitivity as 3% deltaVE/Torr deltaPa(CO(2)). The RTN provides 23% of the overall response. This may be an underestimate. During RTN stimulation Pa(CO(2)) decreases by 4.9 (0.7) Torr (N=5), which may inhibit other chemoreceptor sites. Multiple chemoreceptor sites may interact to provide high sensitivity in systemic hypercapnia and stability during heterogeneous stimulation and inhibition.

Animals↗
PubMed2002

The retrotrapezoid nucleus (RTN): local cytoarchitecture and afferent connections.

The retrotrapezoid nucleus (RTN) provides a source of tonic drive to respiratory neurons and is one of many sites for central chemoreception. Here we evaluate in the rat the local neuronal cytoarchitecture in the RTN histologically 2-4 h after neurobiotin injection and the afferent connections to the RTN 24 h after injection. Our neurobiotin injections often overlapped the RTN and the adjacent neurons of the parapyramidal region, so we group these two regions together in this study. The RTN is made up of small and medium sized neurons and has a low neuronal density compared to other nuclei. The organization of the RTN is reticular in nature and there are prominent small neurons at the ventral medullary border. Adjacent to the pyramids there are medium sized neurons with connections to the raphé pallidus. Major afferent connections include the regions of the dorsal and ventral respiratory groups, the medullary raphé, the contralateral parapyramidal and RTN regions, portions of the nucleus paragigantocellularis lateralis, and portions of the reticular fields. Other sources of input include the Kölliker-fuse nucleus, subceruleus, A5 region, and the paralemniscal zone.

Animals↗
PubMed2002

Ventral medulla pHi measured in vivo by 31P NMR is not regulated during hypercapnia in anesthetized rat.

Chemoreceptors in the ventral medulla contribute to the respiratory response to hypercapnia. Do they 'sense' intracellular pH (pHi)? We measured pHi in the ventral medulla or cortex (control) using 31P-NMR obtained via a novel 3 x 5 mm2 surface coil in anesthetized rats breathing air or 7% CO2. During air breathing over 240 min, pHi decreased slightly from 7.13 +/- 0.02 to 7.05 +/- 0.02 (SEM; n = 5; 2 cortex, 3 ventral medulla). During 180 min of hypercapnia, cortical pHi (n = 4) decreased from 7.17 +/- 0.02 to 6.87 +/- 0.01 by 90 min and recovered by 150 min. Ventral medulla pHi showed no such regulation. It decreased from 7.11 +/- 0.02 to 6.88 +/- 0.02 at 90 min and recovered only after cessation of hypercapnia (n = 5), results consistent with pHi being the chemoreceptor stimulus. However, non-chemoreceptor neurons that contribute to our medullary NMR signal also do not appear to regulate pHi in vitro. Regional differences in pHi regulation between cortex and ventral medulla may be due to both chemosensitive and non-chemosensitive neurons.

Adenosine Triphosphatases↗