Paul A. Gray

28 juin 2012

Department of Anatomy and Neurobiology Washington University, School of Medicine St. Louis, MO

Genetic control of coordination between respiratory unit burst oscillators

Invité par Jean-Charles Viemari

Abstract : Rhythmic behaviors, including breathing, need to coordinate the timing and activity of multiple muscle groups. It is proposed simple rhythms, such as locomotion, are produced by segmentally organized “unit burst oscillators” that generate a coordinated segmental rhythm. Whether this organization is conserved in mammalian respiratory networks is unknown. Isolated perinatal mouse hindbrain/spinal cord preparations generate independent, but strongly coupled, inspiratory (I) and expiratory (E) output from cervical and lumbar motor roots, respectively. Here we show that I/E temporal coordination requires Atoh1 dependent neurons, but that they are not necessary for rhythmogenesis. We tested the obligatory role of Dbx1 and Atoh1 dependent neurons in the generation and coupling of complex respiratory output. Dbx1, but not Atoh1, dependent neurons are necessary for both inspiratory and expiratory output, in vitro. This is consistent with the evolutionarily conserved segmental organization of Dbx1 derived glutamatergic neurons. Without Atoh1, however, normal I/E temporal lags were lost. Further, inspiratory and expiratory oscillators partially decoupled after peptidergic modulation. We propose the respiratory network underlying complex respiratory behaviors consists of independent oscillators whose coupling is controlled by Atoh1 dependent excitatory neurons that play no role in rhythm generation. We propose these data are consistent with proposed segmental oscillator models of simple behavior but provide new insights into the neural mechanisms for the generation of complex behaviors.
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