Mechanisms of respiratory-related rhythmic motor activity and plasticity in the developing avian brain stem - Project Summary
The first motor behaviors produced by vertebrate animals, including humans, begin prior to birth in the form of
embryonic motility and fetal breathing movements. The absence of these embryonic behaviors leads to serious
decrements in muscle and lung function. Early motor behaviors can be studied in vitro in the form of rhythmic
spontaneous neural activity (rSNA) carried in spinal and cranial nerve tracts. rSNA appears as regular
oscillations that self-organize and propagate throughout the developing CNS. Over time, signals that generate
rSNA are anatomically and chemically refined to produce the specific and specialized motor circuits required at
the time of birth, such as inspiration and expiration. Even though rSNA is uniquely positioned to provide
instructions that transform the output and connectivity of neural networks, how rSNA is regulated and how
electrical activity assists in the functional maturation of motor circuits is still speculative. Moreover, the ability of
rSNA to adapt to physiological signals, via homeostatic ionic plasticity, as well as the ramifications of plasticity
for embryonic health, remain unknown. To explore this topic, we will examine the neurophysiology of rSNA as
it transforms into functional breathing-related motor activity within the altricial zebra finch hindbrain. Avian
embryos are an ideal model to test principles of motor system development in all vertebrates, and this project
exploits the in ovo developmental strategy of birds. Oviparity provides unparalleled access to developing
neural circuits throughout incubation. Previously, we showed that breathing-like motor activity could be
recorded day-by-day from its onset through the establishment of ventilation at “birth”. We now know that
inspiratory and expiratory motor phases exhibit changes in temporal pattern during the embryonic period,
which are correlated with changes in transmitter signaling. We found avian breathing circuits are similar to
mammals in their anatomical location and neurotransmitter phenotypes, establishing the bird model as a useful
experimental tool. This renewal proposal will allow us to continue our investigations into the onset,
maintenance and plasticity of branchiomotor rhythms. Aim 1 will test mechanisms of CO2 and pH detection on
breathing-related motor behaviors day-by-day throughout motor circuit development. Published work from our
laboratory shows that pH chemosensitivity influences spontaneous breathing patterns throughout incubation,
but abruptly changes polarity (from inhibition to excitation) once air-breathing is established. We hypothesize
that fetal breathing-related patterns, like adult ventilation, are linked to signals through the maturation of GABA
synaptic transmission and chloride transport. Aim 2 will test how early primordial rhythms maintain intrinsic
activity levels and resist perturbations in neural activity. We will explore periods before air breathing begins.
We will also test whether alterations in rSNA leads to errors in circuit formation and the functional maturation of
the respiratory system both in vitro and in vivo. Importantly, a major goal of this research is to inspire and
expose students at Idaho State University to key research questions in the field of respiratory neurobiology.
