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).
A New Approach to the Hard Problem of Consciousness
David Chalmers’s (1995) hard problem famously states: “It is widely agreed that experience arises from a physical basis, but we have no good explanation of why and how it so arises.” Thomas Nagel (1974) wrote something similar: “If we acknowledge that a physical theory of mind must account for the subjective character of experience, we must admit that no presently available conception gives us a clue about how this could be done.” This presentation will point the way towards the long-sought “good explanation” -- or at least it will provide “a clue”. I will make three points: (1) It is unfortunate that cognitive science took vision as its model example when looking for a ‘neural correlate of consciousness’ because cortical vision (like most cognitive processes) is not intrinsically conscious. There is not necessarily ‘something it is like’ to see. (2) Affective feeling, by contrast, is conscious by definition. You cannot feel something without feeling it. Moreover, affective feeling, generated in the upper brainstem, is the foundational form of consciousness: prerequisite for all the higher cognitive forms. (3) The functional mechanism of feeling explains why and how it cannot go on ‘in the dark’, free of any inner feel. Affect enables the organism to monitor deviations from its expected self-states in uncertain situations and thereby frees homeostasis from the limitations of automatism. As Nagel says, “An organism has conscious mental states if and only if there is something that it is like to be that organism—something it is like for the organism.” Affect literally constitutes the sentient subject.
How the brain comes to balance: Development of postural stability and its neural architecture in larval zebrafish
Maintaining posture is a vital challenge for all freely-moving organisms. As animals grow, their relationship to destabilizing physical forces changes. How does the nervous system deal with this ongoing challenge? Vertebrates use highly conserved vestibular reflexes to stabilize the body. We established the larval zebrafish as a new model system to understand the development of the vestibular reflexes responsible for balance. In this talk, I will begin with the biophysical challenges facing baby fish as they learn to swim. I’ll briefly review published work by David Ehrlich, Ph.D., establishing a fundamental relationship between postural stability and locomotion. The bulk of the talk will highlight unpublished work by Kyla Hamling. She discovered that a small (~50) population of molecularly-defined brainstem neurons called vestibulo-spinal cells act as a nexus for postural development. Her loss-of-function experiments show that these neurons contribute more to postural stability as animals grow older. I’ll end with brief highlights from her ongoing work examining tilt-evoked responses of these neurons using 2-photon imaging and the consequences of downstream activity in the spinal cord using single-objective light-sheet (SCAPE) microscopy