Topic: Ventilation

The peripheral airways in Asthma: significance, assessment, and targeted treatment

The peripheral airways are technically challenging to assess and have been overlooked in the assessment of chronic respiratory diseases such as Asthma, in both the clinical and research space. Evidence of the importance of the small airways in Asthma is building, and small airways dysfunction is implicated in poor Asthma control, airway hyperresponsiveness, and exacerbation risk. The aim of this research was to complete comprehensive global, regional, and spatial assessments of airway function and ventilation in Asthma using physiological and MRI techniques. Specific ventilation imaging (SVI) and Phase resolved functional lung imaging (PREFUL) formed the spatial assessments. SVI uses oxygen as a contrast agent and looks at rate of change in signal to assess ventilation heterogeneity, PREFUL is a completely contrast free technique that uses Fourier decomposition to determine fractional ventilation.

The retrotrapezoid nucleus: an integrative and interoceptive hub in neural control of breathing

In this presentation, we will discuss the cellular and molecular properties of the retrotrapezoid nucleus (RTN), an integrative and interoceptive control node for the respiratory motor system. We will present the molecular profiling that has allowed definitive identification of a cluster of tonically active neurons that provide a requisite drive to the respiratory central pattern generator (CPG) and other pre-motor neurons. We will discuss the ionic basis for steady pacemaker-like firing, including by a large subthreshold oscillation; and for neuromodulatory influences on RTN activity, including by arousal state-dependent neurotransmitters and CO2/H+. The CO2/H+-dependent modulation of RTN excitability represents the sensory component of a homeostatic system by which the brain regulates breathing to maintain blood gases and tissue pH; it relies on two intrinsic molecular proton detectors, both a proton-activated G protein-coupled receptor (GPR4) and a proton-inhibited background K+ channel (TASK-2). We will also discuss downstream neurotransmitter signaling to the respiratory CPG, focusing especially on a newly-identified peptidergic modulation of the preBötzinger complex that becomes activated following birth and the initiation of air breathing. Finally, we will suggest how the cellular and molecular properties of RTN neurons identified in rodent models may contribute to understanding human respiratory disorders, such as congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS).

Collective Ecophysiology and Physics of Social Insects

Collective behavior of organisms creates environmental micro-niches that buffer them from environmental fluctuations e.g., temperature, humidity, mechanical perturbations, etc., thus coupling organismal physiology, environmental physics, and population ecology. This talk will focus on a combination of biological experiments, theory, and computation to understand how a collective of bees can integrate physical and behavioral cues to attain a non-equilibrium steady state that allows them to resist and respond to environmental fluctuations of forces and flows. We analyze how bee clusters change their shape and connectivity and gain stability by spread-eagling themselves in response to mechanical perturbations. Similarly, we study how bees in a colony respond to environmental thermal perturbations by deploying a fanning strategy at the entrance that they use to create a forced ventilation stream that allows the bees to collectively maintain a constant hive temperature. When combined with quantitative analysis and computations in both systems, we integrate the sensing of the environmental cues (acceleration, temperature, flow) and convert them to behavioral outputs that allow the swarms to achieve a dynamic homeostasis.

Generation of a patient specific hIPSC-derived neuronal model for Congenital Central Hypoventilation Syndrome (CCHS)

Identifying therapeutics to treat respiratory deficits associated with the congenital central hypoventilation syndrome (CCHS)