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RATIONALE To study the neural basis of genetic hyperactivity, we measured acute drug responses of mice (Mus domesticus) from four replicate lines that had been selectively bred (23-24 generations) for increased running-wheel activity. OBJECTIVES We tested the hypothesis that the high-running lines would respond differently to cocaine, GBR 12909, and(More)
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 preBötzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is(More)
The ventilatory response to hypoxia depends on the pattern and intensity of hypoxic exposure and involves several physiological mechanisms. These mechanisms differ in their effect (facilitation or depression) on different components of ventilation (tidal volume and frequency) and in their time course (seconds to years). Some mechanisms last long enough to(More)
The hippocampus is important for the acquisition of new memories. It is also one of the few regions in the adult mammalian brain that can generate new nerve cells. The authors tested the hypothesis that voluntary exercise increases neurogenesis and enhances spatial learning in mice selectively bred for high levels of wheel running (S mice). Female S mice(More)
We tested the hypothesis that chronic intermittent hypoxia (CIH) elicits plasticity in the central neural control of breathing via serotonin-dependent effects on the integration of carotid chemoafferent inputs. Adult rats were exposed to 1 week of nocturnal CIH (11-12% O(2)/air at 5 min intervals; 12 hr/night). CIH and untreated rats were then anesthetized,(More)
Repeated isocapnic hypoxia evokes long-term facilitation (LTF) of phrenic nerve activity in rats. We wished to determine: (1) whether hypoxia-induced LTF is serotonin dependent; and (2) whether hypoxia-induced LTF is a property of upper airway motoneurons. Phrenic and hypoglossal nerve activities were recorded in urethane anesthetized, vagotomized,(More)
Plasticity is a hallmark of neural systems, including the neural system controlling breathing (Mitchell and Johnson 2003). Despite its biological and potential clinical significance, our understanding of mechanisms giving rise to any form of respiratory plasticity remains incomplete. Here we discuss recent advances in our understanding of cellular(More)
Phrenic responses to isocapnic hypoxia and hypercapnia were studied using paralyzed vagotomized dogs (either decerebrate or chloralose-anesthetized). The hypoxia-induced increase in phrenic minute activity (PMA) was significantly greater in anesthetized dogs when compared with the response observed in decerebrate dogs. Phrenic responses to hypercapnia were(More)
Intermittent hypoxia causes a form of serotonin-dependent synaptic plasticity in the spinal cord known as phrenic long-term facilitation (pLTF). Here we show that increased synthesis of brain-derived neurotrophic factor (BDNF) in the spinal cord is necessary and sufficient for pLTF in adult rats. We found that intermittent hypoxia elicited(More)
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(More)