The Mammalian Diving Response: Inroads to Its Neural Control.

The mammalian diving response (DR) is a remarkable behavior that was first formally studied by Laurence Irving and Per Scholander in the late 1930s. The DR is called such because it is most prominent in marine mammals such as seals, whales, and dolphins, but nevertheless is found in all mammals studied. It consists generally of breathing cessation (apnea), a dramatic slowing of heart rate (bradycardia), and an increase in peripheral vasoconstriction.

Somatotopy in the Medullary Dorsal Horn As a Basis for Orofacial Reflex Behavior.

The somatotopy of the trigeminocervical complex of the rat was defined as a basis for describing circuitry for reflex behaviors directed through the facial motor nucleus. Thus, transganglionic transport of horseradish peroxidase conjugates applied to individual nerves/peripheral receptive fields showed that nerves innervating oropharyngeal structures projected most rostrally, followed by nerves innervating snout, periocular, and then periauricular receptive fields most caudally. Nerves innervating mucosae or glabrous receptive fields terminated densely in laminae I, II, and V of the trigeminocervical complex, while those innervating hairy skin terminated in laminae I-V.

Injections of Algesic Solutions into Muscle Activate the Lateral Reticular Formation: A Nociceptive Relay of the Spinoreticulothalamic Tract.

Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300 μl) of an algesic solution (6% hypertonic saline, pH 4.

Direct reticular projections of trigeminal sensory fibers immunoreactive to CGRP: potential monosynaptic somatoautonomic projections.

Few trigeminal sensory fibers project centrally beyond the trigeminal sensory complex, with only projections of fibers carried in its sensory anterior ethmoidal (AEN) and intraoral nerves described. Fibers of the AEN project into the brainstem reticular formation where immunoreactivity against substance P and CGRP are found. We investigated whether the source of these peptides could be from trigeminal ganglion neurons by performing unilateral rhizotomies of the trigeminal root and looking for absence of label.

Parasympathetic preganglionic cardiac motoneurons labeled after voluntary diving.

A dramatic bradycardia is induced by underwater submersion in vertebrates. The location of parasympathetic preganglionic cardiac motor neurons driving this aspect of the diving response was investigated using cFos immunohistochemistry combined with retrograde transport of cholera toxin subunit B (CTB) to double-label neurons. After pericardial injections of CTB, trained rats voluntarily dove underwater, and their heart rates (HR) dropped immediately to 95 ± 2 bpm, an 80% reduction.

The mammalian diving response: an enigmatic reflex to preserve life?

The mammalian diving response is a remarkable behavior that overrides basic homeostatic reflexes. It is most studied in large aquatic mammals but is seen in all vertebrates. Pelagic mammals have developed several physiological adaptations to conserve intrinsic oxygen stores, but the apnea, bradycardia, and vasoconstriction is shared with those terrestrial and is neurally mediated.

High-resolution, time-lapse imaging for ecosystem-scale phenotyping in the field.

The high spatial and temporal resolution of data required for high-throughput phenotyping has typically been all but impossible to obtain in field populations of plants. When studies of individual and population genetic variation and microclimate sensor data are combined with phenology data, a landscape-level view of how populations respond to changing environments can be obtained. This chapter will discuss the development of a multi-billion pixel ("gigapixel") camera system that enables the collection of phenology data at up to hourly intervals from in situ plant populations.

Activation of brainstem neurons by underwater diving in the rat.

The mammalian diving response is a powerful autonomic adjustment to underwater submersion greatly affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is mediated by the parasympathetic nervous system, arterial blood pressure is mediated via the sympathetic system and still other circuits mediate the respiratory changes. In the present study we investigate the cardiorespiratory responses and the brainstem neurons activated by voluntary diving of trained rats, and, compare them to control and swimming animals which did not dive.

Persistence of the nasotrigeminal reflex after pontomedullary transection.

Most behaviors have numerous components based on reflexes, but the neural circuits driving most reflexes rarely are documented. The nasotrigeminal reflex induced by stimulating the nasal mucosa causes an apnea, a bradycardia, and variable changes in mean arterial blood pressure (MABP). In this study we tested the nasotrigeminal reflex after transecting the brainstem at the pontomedullary junction.

A trigeminoreticular pathway: implications in pain.

Neurons in the caudalmost ventrolateral medulla (cmVLM) respond to noxious stimulation. We previously have shown most efferent projections from this locus project to areas implicated either in the processing or modulation of pain. Here we show the cmVLM of the rat receives projections from superficial laminae of the medullary dorsal horn (MDH) and has neurons activated with capsaicin injections into the temporalis muscle.

The effect of heliox treatment in a rat model of focal transient cerebral ischemia.

Manipulation of inhaled gases during ischemia/reperfusion is a potential novel therapy for acute stroke. We previously found that treatment with a mixture of 70%/30% helium/oxygen (heliox) or 100% oxygen protects the brain against acute focal ischemia-reperfusion injury. This study evaluates the potential neuro-protective effects of delayed heliox treatment and its dose response effects in a rat transient focal cerebral ischemia model.

The neurotoxicity of DOPAL: behavioral and stereological evidence for its role in Parkinson disease pathogenesis.

Background: The etiology of Parkinson disease (PD) has yet to be fully elucidated. We examined the consequences of injections of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite of dopamine, into the substantia nigra of rats on motor behavior and neuronal survival.

Methods/principal Findings: A total of 800 nl/rat of DOPAL (1 µg/200 nl) was injected stereotaxically into the substantia nigra over three sites while control animals received similar injections of phosphate buffered saline.

Morphine modulation of thrombospondin levels in astrocytes and its implications for neurite outgrowth and synapse formation.

Opioid receptor signaling via EGF receptor (EGFR) transactivation and ERK/MAPK phosphorylation initiates diverse cellular responses that are cell type-dependent. In astrocytes, multiple μ opioid receptor-mediated mechanisms of ERK activation exist that are temporally distinctive and feature different outcomes. Upon discovering that chronic opiate treatment of rats down-regulates thrombospondin 1 (TSP1) expression in the nucleus accumbens and cortex, we investigated the mechanism of action of this modulation in astrocytes.

Cardiorespiratory and neural consequences of rats brought past their aerobic dive limit.

The mammalian diving response is a dramatic autonomic adjustment to underwater submersion affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is known to be modulated by the parasympathetic nervous system, arterial blood pressure is modulated via the sympathetic system, and still other circuits modulate the respiratory changes. In the present study, we investigate the submergence of rats brought past their aerobic dive limit, defined as the diving duration beyond which blood lactate concentration increases above resting levels.

The rat: a laboratory model for studies of the diving response.

Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species.

Distinct central representations for sensory fibers innervating either the conjunctiva or cornea of the rat.

The laminar sheet of epithelium (e.g., skin and mucous membrane) enclosing our bodies is represented in the dorsal horns of the medulla and spinal cord.

Pressor responses to nasal stimulation are unaltered after disrupting the CPA.

Stimulation of either the caudal pressor area (CPA) in the most caudal ventrolateral medulla with glutamate, or the nasal mucosa with ammonia vapors, induces an increase in mean arterial blood pressure (MABP). In the present study, we determined if neurons in the CPA serve as a relay for the increase in MABP seen after nasal stimulation. Ammonia vapors stimulated the nasal mucosa of rats anesthetized with either urethane alone or ketamine/xylazine and urethane to induce an increase in MABP, a bradycardia, and an apnea.

Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopamine (DA) neurons and the presence of alpha-synuclein (AS) aggregates as Lewy bodies (LBs) in the remaining substantia nigra (SN) neurons. A continuing puzzle in studying PD pathogenesis is that although AS is expressed throughout the brain, LBs and selective dopaminergic cell loss lead to characteristic clinical signs of PD, suggesting that there is a link between AS aggregation and DA metabolism. One potential candidate for this link is the monoamine oxidase (MAO) metabolite of DA, 3,4-dihydroxyphenylacetaldehyde (DOPAL), as neither DA nor DA metabolites other than DOPAL are toxic to SN neurons at physiological concentrations.

Heliox and oxygen reduce infarct volume in a rat model of focal ischemia.

Normobaric hyperoxia treatment has recently been demonstrated to be remarkably beneficial in acute focal ischemia. The present study compared hyperoxia treatment with a novel heliox treatment. Adult male rats breathed 30% oxygen and 70% nitrogen (control group), 100% oxygen (hyperoxia group), or 30% oxygen and 70% helium (heliox group) during a middle cerebral artery occlusion for 2 h and a 1-hour reperfusion (n=6 in each group).

Brainstem projections from recipient zones of the anterior ethmoidal nerve in the medullary dorsal horn.

Stimulation of the anterior ethmoidal nerve or the nasal mucosa induces cardiorespiratory responses similar to those seen in diving mammals. We have utilized the transganglionic transport of a cocktail of horseradish peroxidase conjugates and anterograde and retrograde tract tracing techniques to elucidate pathways which may be important for these responses in the rat. Label was seen throughout the trigeminal sensory complex after the horseradish peroxidase conjugates were applied to the anterior ethmoidal nerve peripherally.

The central termination of sensory fibers from nerves to the gastrocnemius muscle of the rat.

Peripheral nerves innervating muscles have sensory fibers that relay information into the CNS information about proprioception, pain, and the metabolic state of the muscle. The present study shows the primary afferent projections into the spinal cord of the nerves innervating the gastrocnemius muscle of the rat using the transganglionic transport of a cocktail of horseradish peroxidase (HRP) conjugated to cholera toxin and wheat germ agglutinin; these markers have been shown to label large and small fibers, respectively. A dense projection into lamina I of the lumbar dorsal horn and a more moderate projection into lamina V were seen.

Engraftment of freshly isolated or cultured human umbilical cord blood cells and the effect of cyclosporin A on the outcome.

Human umbilical cord blood (HUCB) is a potentially valuable resource for cell therapy. The present study investigated the short-term survival of intrastriatal grafts of either freshly isolated or cultured HUCB cells and the effect of the immunosuppressive agent cyclosporin A (CSA) in host rat brains. The group injected with either freshly isolated or cultured HUCB cells was subdivided into CSA or saline controls.

Defining projections from the caudal pressor area of the caudal ventrolateral medulla.

We previously defined a functional area in the caudal medulla oblongata that elicits an increase in arterial pressure when stimulated (Sun and Panneton [2002] Am. J. Physiol.

Activation of brainstem catecholaminergic neurons during voluntary diving in rats.

Underwater submergence produces a complex autonomic response that includes apnea, a parasympathetically-mediated bradycardia, and a sympathetically-mediated increase in total peripheral resistance (TPR). The present study was designed to identify brainstem catecholaminergic neurons that may be involved in producing the increased TPR during underwater submergence. Twelve male Sprague-Dawley rats were trained to voluntarily dive 5 m through an underwater maze.

The caudal pressor area of the rat: its precise location and projections to the ventrolateral medulla.

Investigators have demonstrated pressor areas in the medullas of various species. The present study precisely localized the pressor area in the caudal medulla of the rat and determined its projections to the caudal and rostral ventrolateral medulla. The caudal medulla first was mapped grossly in rats with injections (30 nl) of glutamate (30-, 15-, and 7.