Figure 5. Activation of 5-HT_1A receptors does not restore rhythmic phrenic activity after complete blockade of synaptic inhibition.

Aa-e and Ba-c illustrate sequences of drug applications in two different experiments. Aa, control recordings before injection of drugs. Ab, successive application of strychnine (Stry, 50 μm) and bicuculline (Bic, 50 μm) induced a regular apneustic breathing pattern characterized by a prolongation of the inspiratory burst duration. Ac, following development of such apneustic activity pattern, an injection of 8-OH-DPAT (50 μm; a 5-HT_1A agonist) restored rhythmic phrenic activity, its bursting occurring at higher frequencies. This effect was only transient and vanished after 1-2 min. Ad, additional injections of strychnine (100 μm) and bicuculline (100 μm) completely abolished rhythmic bursting of phrenic activity. Ae, subsequent injections of 8-OH-DPAT (50 μm) led to increased fluctuations of tonic phrenic activity, which for short periods, but not persistently, could appear rhythmic. Ba, ipsilateral strychnine injection (100 μm) reduced the amplitude and the duration of phrenic burst activity without changing the early inspiratory burst pattern as can be seen in the superimposed traces on the right. Bb, inspiratory burst duration was dramatically increased (arrow) and the slope of phrenic burst discharge slowed after additional injection of bicuculline (50 μm). This led to an apneustic activity pattern. Bicuculline also reduced the amplitude at onset of phrenic burst activity. Bc, within the following few minutes, subsequent activation of 5-HT_1A receptors on PBC cells by 8-OH-DPAT (50 μm) reversed the apneustic activity pattern. Bursts again showed a steady augmentation of inspiratory activity and their durations were reduced to almost normal (arrow). When rhythmic phrenic activity was blocked after a longer latency, 8-OH-DPAT injections were ineffective (see Ae). PN, original phrenic activity; PN_a, moving average of phrenic activity.