Role of synaptic inhibition in turtle respiratory rhythm generation

In vitro brainstem and brainstem-spinal cord preparations were used to determine the role of synaptic inhibition in respiratory rhythm generation in adult turtles. Bath application of bicuculline (a GABA(A) receptor antagonist) to brainstems increased hypoglossal burst frequency and amplitude, with peak discharge shifted towards the burst onset. Strychnine (a glycine receptor antagonist) increased amplitude and frequency, and decreased burst duration, but only at relatively high concentrations (10-100 microM). Rhythmic activity persisted during combined bicuculline and strychnine application (50 microM each) with increased amplitude and frequency, decreased burst duration, and a rapid onset-decrementing burst pattern. The bicuculline-strychnine rhythm frequency decreased during mu-opioid receptor activation or decreased bath P(C)(O(2)). Synaptic inhibition blockade in the brainstem of brainstem-spinal cord preparations increased burst amplitude in spinal expiratory (pectoralis) nerves and nearly abolished spinal inspiratory activity (serratus nerves), suggesting that medullary expiratory motoneurons were mainly active. Under conditions of synaptic inhibition blockade in vitro, the turtle respiratory network was able to produce a rhythm that was sensitive to characteristic respiratory stimuli, perhaps via an expiratory (rather than inspiratory) pacemaker-driven mechanism. Thus, these data indicate that the adult turtle respiratory rhythm generator has the potential to operate in a pacemaker-driven manner.