I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

▪ Abstract Breathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBotzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.

Breathing: Rhythmicity, plasticity, chemosensitivity

Time domains of the hypoxic ventilatory response.

Prevalence and risk factors for sleep-disordered breathing in 8- to 11-year-old children: association with race and prematurity.

Serotonergic neurons in the medulla have recently been shown to be sensors of carbon dioxide and pH. There is compelling evidence that the co-release of serotonin, substance P and thyrotropin-releasing hormone from these neurons stimulates the neural network that controls breathing at numerous sites using many different mechanisms. Serotonergic neurons in the midbrain are also chemosensitive, and might mediate non-respiratory responses to increased carbon dioxide, such as arousal. This role in control of pH homeostasis could provide a neurobiological explanation for the link between changes in the serotonin system and sudden infant death syndrome (SIDS).

Serotonergic neurons as carbon dioxide sensors that maintain pH homeostasis.

Intermittent hypoxia elicits long-term facilitation (LTF), a persistent augmentation (hours) of respiratory motor output. Considerable recent progress has been made toward an understanding of the mechanisms and manifestations of this potentially important model of respiratory plasticity. LTF is elicited by intermittent but not sustained hypoxia, indicating profound pattern sensitivity in its underlying mechanism. During intermittent hypoxia, episodic spinal serotonin receptor activation initiates cell signaling events, increasing spinal protein synthesis. One associated protein is brain-derived neurotrophic factor, a neurotrophin implicated in several forms of synaptic plasticity. Our working hypothesis is that increased brain-derived neurotrophic factor enhances glutamatergic synaptic currents in phrenic motoneurons, increasing their responsiveness to bulbospinal inspiratory inputs. LTF is heterogeneous among respiratory outputs, differs among experimental preparations, and is influenced by age, gender, and genetics. Furthermore, LTF is enhanced following chronic intermittent hypoxia, indicating a degree of metaplasticity. Although the physiological relevance of LTF remains unclear, it may reflect a general mechanism whereby intermittent serotonin receptor activation elicits respiratory plasticity, adapting system performance to the ever-changing requirements of life.

Invited Review: Intermittent hypoxia and respiratory plasticity

1. This study was designed to test the hypothesis that perinatal suppression of peripheral arterial chemoreceptor inputs attenuates the hypoxic ventilatory response in adult rats. Perinatal suppression of peripheral chemoreceptor activity was achieved by exposing rats to hyperoxia throughout the first month of life. 2. Late-gestation pregnant rats were housed in a 60% O2 environment, exposing the pups to hyperoxia from several days prior to birth until they were returned to normoxia on postnatal day 28. These perinatally treated rats were then reared to adulthood (3-5 months old) in normoxia. In addition to the mother rats, adult male rats were also exposed to hyperoxia, creating an adult-treated control group. Two to four months after the hyperoxic exposure, treated rats were compared with untreated male rats of similar age. 3. A whole-body, flow-through plethysmograph was used to measure hypoxic and hypercapnic ventilatory responses of the unanaesthetized adult rats. In moderate hypoxia (arterial oxygen partial pressure, Pa,O2 approximately 48 mmHg). VE (minute ventilation) and the ratio VE/VCO2 (ventilation relative to CO2 production) increased by 16.7 +/- 4.0 and 35.4 +/- 3.4%, respectively, in perinatal-treated rats (means +/- S.E.M.), but increased more in untreated control rats (51.4 +/- 2.8 and 83.1 +/- 4.3%; both P < 10(-6)). 4. In contrast to the impaired hypoxic ventilatory response, ventilatory responses to hypercapnia (5% CO2) were similar between untreated control and perinatal-treated rats. 5. Impaired hypoxic responsiveness was unique to the perinatal-treated rats since hypoxic ventilatory responses were not attenuated in adult-treated rats. 6. The results indicate that ventilatory responses to hypoxaemia are greatly attenuated in adult rats that had experienced hyperoxia during their first month of life, and suggest that normal hypoxic ventilatory control mechanisms are susceptible to developmental plasticity.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1996.sp021616

Attenuation of the hypoxic ventilatory response in adult rats following one month of perinatal hyperoxia.

We tested two hypotheses: 1) that the spontaneous enhancement of phrenic motor output below a C2 spinal hemisection (C2HS) is associated with plasticity in ventrolateral spinal inputs to phrenic mo...

Recovery of phrenic activity and ventilation after cervical spinal hemisection in rats

Developmental plasticity of the hypoxic ventilatory response

Exposing newborn rats to postnatal hyperoxia (60% O2) for 1-4 wk attenuates the ventilatory and phrenic nerve responses to acute hypoxia in adult rats The goal of this research was to increase our

E. B. Olson

Papers

Invited Review: Intermittent hypoxia and respiratory plasticity

Attenuation of the hypoxic ventilatory response in adult rats following one month of perinatal hyperoxia.

Recovery of phrenic activity and ventilation after cervical spinal hemisection in rats

Developmental plasticity of the hypoxic ventilatory response

Adult carotid chemoafferent responses to hypoxia after 1, 2, and 4 wk of postnatal hyperoxia