It is well‐documented that feedforward cardiovascular responses occur at the onset of exercise, but it is unclear if such responses are associated with other types of movements. In this study, we tested the hypothesis that feedforward cardiovascular responses occur when a passive (imposed) 60° head‐up tilt is anticipated, such that changes in heart rate and carotid artery blood flow (CBF) commence prior to the onset of the rotation. A light cue preceded head‐up tilts by 10 sec, and heart rate and CBF were determined for 5‐sec time periods prior to and during tilts. Even after these stimuli were provided for thousands of trials spanning several months, no systematic changes in CBF and heart rate occurred prior to tilts, and variability in cardiovascular adjustments during tilt remained substantial over time. We also hypothesized that substitution of 20° for 60° tilts in a subset of trials would result in exaggerated cardiovascular responses (as animals expected 60° tilts), which were not observed. These data suggest that cardiovascular adjustments during passive changes in posture are mainly elicited by feedback mechanisms, and that anticipation of passive head‐up tilts does not diminish the likelihood that a decrease in carotid blood flow will occur during the movements.

The vestibular system contributes to regulating sympathetic nerve activity and blood pressure. Initial studies in decerebrate animals showed that neurons in the rostral ventrolateral medulla (RVLM) respond to small-amplitude (<10°) rotations of the body, as in other brain areas that process vestibular signals, although such movements do not affect blood distribution in the body. However, a subsequent experiment in conscious animals showed that few RVLM neurons respond to small-amplitude movements. This study tested the hypothesis that RVLM neurons in conscious animals respond to signals from the vestibular otolith organs elicited by large-amplitude static tilts. The activity of approximately one-third of RVLM neurons whose firing rate was related to the cardiac cycle, and thus likely received baroreceptor inputs, was modulated by vestibular inputs elicited by 40° head-up tilts in conscious cats, but not during 10° sinusoidal rotations in the pitch plane that affected the activity of neurons in brain regions providing inputs to the RVLM. These data suggest the existence of brain circuitry that suppresses vestibular influences on the activity of RVLM neurons and the sympathetic nervous system unless these inputs are physiologically warranted. We also determined that RVLM neurons failed to respond to a light cue signaling the movement, suggesting that feedforward cardiovascular responses do not occur before passive movements that require cardiovascular adjustments.

Key pointsr Reduced computational models are used to test effects of loss of inhibition to the Kölliker-Fuse nucleus (KFn).r Three reduced computational models that simulate eupnoeic and vagotomized respiratory rhythms are considered.r All models exhibit the emergence of respiratory perturbations associated with Rett syndrome as inhibition to the KFn is diminished.r Simulations suggest that application of 5-HT 1A agonists can mitigate the respiratory pathology. r The three models can be distinguished and tested based on their predictions about connections and dynamics within the respiratory circuit and about effects of perturbations on certain respiratory neuron populations.Abstract Rett syndrome (RTT) is a developmental disorder that can lead to respiratory disturbances featuring prolonged apnoeas of variable durations. Determining the mechanisms underlying these effects at the level of respiratory neural circuits would have significant implications for treatment efforts and would also enhance our understanding of respiratory rhythm generation and control. While experimental studies have suggested possible factors contributing to the respiratory patterns of RTT, we take a novel computational approach to the investigation of RTT, which allows for direct manipulation of selected system parameters and testing of specific hypotheses. Specifically, we present three reduced computational models, developed using an established framework, all of which successfully simulate respiratory outputs across eupnoeic and vagotomized conditions. All three models show that loss of inhibition to the Kölliker-Fuse nucleus reproduces the key respiratory alterations associated with RTT and, as suggested experimentally, that effects of 5-HT 1A agonists on the respiratory neural circuit suffice Sam Wittman graduated from the University of Pittsburgh in 2017 with BS degrees in mathematical biology and neuroscience. As an undergraduate, he performed modelling research on the neural basis of Rett syndrome under Dr Jonathan Rubin, and he worked in the vestibular electrophysiology lab of Dr Bill Yates and Dr Andrew McCall. He is currently pursuing a MS in S. Wittman and others J Physiol 597.10to alleviate this respiratory pathology. Each of the models makes distinct predictions regarding the neuronal populations and interactions underlying these effects, suggesting natural directions for future experimental testing.

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