Reorganisation of respiratory network activity after loss of glycinergic inhibition

gamma -Aminobutyric acid (GABA)-ergic and glycinergic inhibition is believe d to play a major role in the respiratory network. In the present study we tested whether specific blockade of glycinergic inhibition resulted in chan ges in respiratory network interaction and function. Using the working hear t-brainstem preparation from adult mice, we recorded phrenic nerve activity and the activity of different types of respiratory neurones located in the ventrolateral medulla. Strychnine (0.03-0.3 muM) was given systemically to block glycine receptors (Gly-R). During exposure to strychnine, post-inspi ratory (PI) neurones shifted their onset of discharge into the inspiratory phase. As a consequence, the post-inspiratory phase failed and the rhythm c hanged from a three-phase cycle (inspiration, post-inspiration, expiration, with a frequency of about. 0.24 Hz) to a faster, two-phased cycle (inspira tion expiration, frequency about 0.41 Hz). Inspiratory and expiratory neuro nes altered their augmenting membrane potential pattern to a rapidly peakin g pattern. Smaller voltage oscillations at approximately 10 Hz and consisti ng of excitatory and inhibitory postsynaptic potential sequences occurred d uring the expiratory interval. Due to their high frequency and low amplitud e, such oscillations would be inadequate for lung ventilation. We conclude that, under physiological conditions, glycinergic inhibition does indeed pl ay a major role in the generation of a normal respiratory rhythm in adult m ice. After failure of glycinergic inhibition a faster respiratory rhythm se ems to operate through reciprocal GABAergic inhibition between inspiratory and expiratory neurones, while phase switching is organised by activation o f intrinsic membrane properties.