A Leptin-Mediated Neural Mechanism Linking Breathing to Metabolism.

Breathing is coupled to metabolism. Leptin, a peptide mainly secreted in proportion to adipose tissue mass, increases energy expenditure with a parallel increase in breathing. We demonstrate that optogenetic activation of LepRb neurons in the nucleus of the solitary tract (NTS) mimics the respiratory stimulation after systemic leptin administration.

Activation of astrocytic PAR1 receptors in the rat nucleus of the solitary tract regulates breathing through modulation of presynaptic TRPV1.

Key Points: In the rat nucleus of the solitary tract (NTS), activation of astrocytic proteinase-activated receptor 1 (PAR1) receptors leads to potentiation of neuronal synaptic activity by two mechanisms, one TRPV1-dependent and one TRPV1-independent. PAR1-dependent activation of presynaptic TRPV1 receptors facilitates glutamate release onto NTS neurons. The TRPV1-dependent mechanism appears to rely on astrocytic release of endovanilloid-like molecules.

pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract.

The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission.

Systemic leptin produces a long-lasting increase in respiratory motor output in rats.

Leptin decreases food intake and increases energy expenditure. Leptin administration into the CNS of mice or rats increases alveolar ventilation and dysfunction in leptin signaling has been implicated in the hypoventilation that can accompany obesity. An increase in CO(2) chemosensitivity has been implicated in this response but it is unclear whether ventilation is augmented when PCO(2) is maintained constant.

Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract.

Cellular mechanisms of central pH chemosensitivity remain largely unknown. The nucleus of the solitary tract (NTS) integrates peripheral afferents with central pathways controlling breathing; NTS neurons function as central chemosensors, but only limited information exists concerning the ionic mechanisms involved. Acid-sensing ion channels (ASICs) mediate chemosensitivity in nociceptive terminals, where pH values ∼6.

Biocompatible nanoscale dispersion of single-walled carbon nanotubes minimizes in vivo pulmonary toxicity.

Excitement surrounding the attractive physical and chemical characteristics of single walled carbon nanotubes (SWCNTs) has been tempered by concerns regarding their potential health risks. Here we consider the lung toxicity of nanoscale dispersed SWCNTs (mean diameter approximately 1 nm). Because dispersion of the SWCNTs increases their aspect ratio relative to as-produced aggregates, we directly test the prevailing hypothesis that lung toxicity associated with SWCNTs compared with other carbon structures is attributable to the large aspect ratio of the individual particles.

Overview: the neurochemistry of respiratory control.

This special issue of Respiratory Physiology and Neurobiology surveys a broad range of topics focused on the neurochemical control of breathing. A variety of approaches have integrated the neurochemistry of breathing with the physiology of individual neurons, with the neuroanatomy of brainstem and forebrain respiratory circuits, and with the clinical pathology of respiratory disorders all of which has been fueled by the ongoing explosion of information in the molecular biology of the nervous system. Accordingly, substantial progress has identified neurotransmitters, neuromodulators, receptors, signaling cascades, trophic factors, hormones, and genes mediating normal and pathological breathing.

The chemical neuroanatomy of breathing.

The chemical neuroanatomy of breathing must ultimately encompass all the various neuronal elements physiologically identified in brainstem respiratory circuits and their apparent aggregation into "compartments" within the medulla and pons. These functionally defined respiratory compartments in the brainstem provide the major source of input to cranial motoneurons controlling the airways, and to spinal motoneurons activating inspiratory and expiratory pump muscles. This review provides an overview of the neuroanatomy of the major compartments comprising brainstem respiratory circuits, and a synopsis of the transmitters used by their constituent respiratory neurons.

Central pathways of pulmonary and lower airway vagal afferents.

Lung sensory receptors with afferent fibers coursing in the vagus nerves are broadly divided into three groups: slowly (SAR) and rapidly (RAR) adapting stretch receptors and bronchopulmonary C fibers. Central terminations of each group are found in largely nonoverlapping regions of the caudal half of the nucleus of the solitary tract (NTS). Second order neurons in the pathways from these receptors innervate neurons located in respiratory-related regions of the medulla, pons, and spinal cord.

Sodium currents in medullary neurons isolated from the pre-Bötzinger complex region.

The pre-Bötzinger complex (preBötC) in the ventrolateral medulla contains interneurons important for respiratory rhythm generation. Voltage-dependent sodium channels mediate transient current (I(NaT)), underlying action potentials, and persistent current (I(NaP)), contributing to repetitive firing, pacemaker properties, and the amplification of synaptic inputs. Voltage-clamp studies of the biophysical properties of these sodium currents were conducted on acutely dissociated preBötC region neurons.

Parabrachial-lateral pontine neurons link nociception and breathing.

We investigated the role of the parabrachial complex in cutaneous nociceptor-induced respiratory stimulation in chloralose-urethane anesthetized, vagotomized rats. Noxious stimulation (mustard oil, MO) applied topically to a forelimb or hindlimb enhanced the peak amplitude of the integrated phrenic nerve discharge and, with forelimb application, increased phrenic nerve burst frequency. Bilateral inactivation of neural activity in the parabrachial complex with injection of the GABA agonist muscimol (3nl) markedly attenuated the response to MO application.

Pontine influences on breathing: an overview.

Historical and contemporary views of the functional organization of the lateral pontine regions influencing breathing are reviewed. In vertebrates, the rhombencephalon generates a breathing rhythm and detailed motor pattern that persist throughout life. Key to this process is an essentially continuous column of neurons extending from the spino-medullary border through the ventrolateral medulla, continuing through the ventral pons and arcing into the dorsolateral medulla.

Concept mapping in pulmonary physiology using pathfinder scaling.

This three-part article begins with a brief presentation of a framework that describes different approaches to conduct and report research on expert knowledge. The framework contrasts direct vs. indirect approaches and provides examples of each.

Resurgent Na currents in four classes of neurons of the cerebellum.

Action potential firing rates are generally limited by the refractory period, which depends on the recovery from inactivation of voltage-gated Na channels. In cerebellar Purkinje neurons, the kinetics of Na channels appear specialized for rapid firing. Upon depolarization, an endogenous open-channel blocker rapidly terminates current flow but prevents binding of the "fast" inactivation gate.

Intrinsic bursting activity in the pre-Bötzinger complex: role of persistent sodium and potassium currents.

Computational models of single pacemaker neuron and neural population in the pre-Bötzinger Complex (pBC) were developed based on the previous models by Butera et al. (1999a,b). Our modeling study focused on the conditions that could define endogenous bursting vs.

Sodium currents in neurons from the rostroventrolateral medulla of the rat.

Rapidly inactivating and persistent sodium currents have been characterized in acutely dissociated neurons from the area of rostroventrolateral medulla that included the pre-Bötzinger Complex. As demonstrated in many studies in vitro, this area can generate endogenous rhythmic bursting activity. Experiments were performed on neonate and young rats (P1-15).