David H. McDougal

Bio: David H. McDougal is an academic researcher from Pennington Biomedical Research Center. The author has contributed to research in topics: Hypoglycemia & Leptin. The author has an hindex of 10, co-authored 22 publications receiving 1197 citations. Previous affiliations of David H. McDougal include University of Alabama at Birmingham.

Autonomic control of the eye

Abstract: The autonomic nervous system influences numerous ocular functions. It does this by way of parasympathetic innervation from postganglionic fibers that originate from neurons in the ciliary and pterygopalatine ganglia, and by way of sympathetic innervation from postganglionic fibers that originate from neurons in the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction, respectively. Superior cervical ganglion neurons project to the dilator pupillae muscle of the iris to control pupil dilation. Ocular blood flow is controlled both via direct autonomic influences on the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as via indirect influences on retinal blood flow. In mammals, this vasculature is innervated by vasodilatory fibers from the pterygopalatine ganglion, and by vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure is regulated primarily through the balance of aqueous humor formation and outflow. Autonomic regulation of ciliary body blood vessels and the ciliary epithelium is an important determinant of aqueous humor formation; autonomic regulation of the trabecular meshwork and episcleral blood vessels is an important determinant of aqueous humor outflow. These tissues are all innervated by fibers from the pterygopalatine and superior cervical ganglia. In addition to these classical autonomic pathways, trigeminal sensory fibers exert local, intrinsic influences on many of these regions of the eye, as well as on some neurons within the ciliary and pterygopalatine ganglia.

Low protein-induced increases in FGF21 drive UCP1-dependent metabolic but not thermoregulatory endpoints.

Abstract: Dietary protein restriction increases adipose tissue uncoupling protein 1 (UCP1), energy expenditure and food intake, and these effects require the metabolic hormone fibroblast growth factor 21 (FGF21). Here we test whether the induction of energy expenditure during protein restriction requires UCP1, promotes a resistance to cold stress, and is dependent on the concomitant hyperphagia. Wildtype, Ucp1-KO and Fgf21-KO mice were placed on control and low protein (LP) diets to assess changes in energy expenditure, food intake and other metabolic endpoints. Deletion of Ucp1 blocked LP-induced increases in energy expenditure and food intake, and exacerbated LP-induced weight loss. While LP diet increased energy expenditure and Ucp1 expression in an FGF21-dependent manner, neither LP diet nor the deletion of Fgf21 influenced sensitivity to acute cold stress. Finally, LP-induced energy expenditure occurred even in the absence of hyperphagia. Increased energy expenditure is a primary metabolic effect of dietary protein restriction, and requires both UCP1 and FGF21 but is independent of changes in food intake. However, the FGF21-dependent increase in UCP1 and energy expenditure by LP has no effect on the ability to acutely respond to cold stress, suggesting that LP-induced increases in FGF21 impact metabolic but not thermogenic endpoints.

Vagal afferent stimulation activates astrocytes in the nucleus of the solitary tract via AMPA receptors: evidence of an atypical neural-glial interaction in the brainstem.

Abstract: The nucleus of the solitary tract (NST), located in the dorsomedial medulla, is the site of visceral sensory modulation of a variety of homeostatic reflexes. Given recent advancements in the understanding of active regulation of synaptic information flow by astrocytes, we sought to determine whether afferent sensory inputs to NST neurons also activates NST astrocytes. Using confocal, live-cell calcium imaging of brainstem slices, we investigated the possibility that stimulation of vagal sensory afferents, the major sensory input into the NST, activated NST astrocytes, as indicated by increases in astrocytic intracellular calcium concentrations ([Ca2+]i). Astrocytes and neurons were preloaded with the calcium reporter dye Calcium Green, and astrocytes were selectively stained by sulforhodamine 101. Electrical stimulation of vagal afferent axons produced rapid increases in [Ca2+]i in NST astrocytes as well as neurons. Surprisingly, this effect on astrocytes was blocked by the AMPA receptor antagonist NBQX and was unaffected by antagonism of NMDA and metabotropic glutamate receptors. Bath application of AMPA also activated astrocytes. This activation was dependent on extracellular Ca2+ influx through both typical AMPA receptors and calcium-permeable AMPA receptors. This AMPA-mediated Ca2+ influx was further amplified by actions of the ryanodine receptor by way of calcium-induced calcium release. Our immunohistochemical staining of NST cells further verified the presence of the AMPAR subunit GluR1 on astrocytes. These observations suggest that NST astrocytes may be active participants in the regulation of autonomic reflexes even in the normal, healthy state.

Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex.

Abstract: Rapid variations in cortical state during wakefulness have a strong influence on neural and behavioural responses and are tightly coupled to changes in pupil size across species. However, the physiological processes linking cortical state and pupil variations are largely unknown. Here we demonstrate that these rapid variations, during both quiet waking and locomotion, are highly correlated with fluctuations in the activity of corticopetal noradrenergic and cholinergic projections. Rapid dilations of the pupil are tightly associated with phasic activity in noradrenergic axons, whereas longer-lasting dilations of the pupil, such as during locomotion, are accompanied by sustained activity in cholinergic axons. Thus, the pupil can be used to sensitively track the activity in multiple neuromodulatory transmitter systems as they control the state of the waking brain.

Supporting Online Material for Astrocytes Potentiate Transmitter Release at Single Hippocampal Synapses

Abstract: Astrocytes play active roles in brain physiology. They respond to neurotransmitters and modulate neuronal excitability and synaptic function. However, the influence of astrocytes on synaptic transmission and plasticity at the single synapse level is unknown. Ca2+ elevation in astrocytes transiently increased the probability of transmitter release at hippocampal area CA3-CA1 synapses, without affecting the amplitude of synaptic events. This form of short-term plasticity was due to the release of glutamate from astrocytes, a process that depended on Ca2+ and soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) protein and that activated metabotropic glutamate receptors (mGluRs). The transient potentiation of transmitter release became persistent when the astrocytic signal was temporally coincident with postsynaptic depolarization. This persistent plasticity was mGluR-mediated but N-methyl-d-aspartate receptor–independent. These results indicate that astrocytes are actively involved in the transfer and storage of synaptic information.

Physiology of the Gastrointestinal Tract

Abstract: Of easily readable size and presenting its material in an attractive format, this work is oriented toward the medical student. It covers the subject under major headings of splanchnic circulation, motor mechanisms, secretion, digestion, and absorption. The bibliography is brief, and controversial points generally are passed over. Although opinions differ over what the medical student should be taught and how material should be presented, coverage certainly offers an adequate background in most areas of gastrointestinal physiology. Hepatic physiology, however, is incompletely examined, and the authors seem not to have decided how to approach this complicated subject. Perhaps hepatic physiology, now so extensive, can be covered adequately only in a separate volume. Some of the material is presented and discussed in a confusing or inadequate manner, especially for a book designed as an introductory text for students. For example, the authors mention results obtained by using a Pavlov pouch, but they

Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality.

Abstract: Objectives Specifications and standards for lighting installations in occupational settings are based on the spectral sensitivity of the classical visual system and do not take into account the recently discovered melanopsin-based, blue-light-sensitive photoreceptive system. The authors investigated the effects of exposure to blue-enriched white light during daytime workhours in an office setting. Methods The experiment was conducted on 104 white-collar workers on two office floors. After baseline assessments under existing lighting conditions, every participant was exposed to two new lighting conditions, each lasting 4 weeks. One consisted of blue-enriched white light (17 000 K) and the other of white light (4000 K). The order was balanced between the floors. Questionnaire and rating scales were used to assess alertness, mood, sleep quality, performance, mental effort, headache and eye strain, and mood throughout the 8-week intervention. Results Altogether 94 participants [mean age 36.4 (SD 10.2) years] were included in the analysis. Compared with white light (4000 K), blue-enriched white light (17 000 K) improved the subjective measures of alertness (P<0.0001), positive mood (P=0.0001), performance (P<0.0001), evening fatigue (P=0.0001), irritability (P=0.004), concentration (P<0.0001), and eye discomfort (P=0.002). Daytime sleepiness was reduced (P=0.0001), and the quality of subjective nocturnal sleep (P=0.016) was improved under blue-enriched white light. When the participants’ expectation about the effect of the light treatments was entered into the analysis as a covariate, significant effects persisted for performance, alertness, evening fatigue, irritability, difficulty focusing, concentrating, and blurred vision. Conclusions Exposure to blue-enriched white light during daytime workhours improves subjective alertness, performance, and evening fatigue.