LATE EXPIRATORY INHIBITION OF STAGE-2 EXPIRATORY NEURONS IN THE CAT -A CORRELATE OF EXPIRATORY TERMINATION

1. Intracellular recordings were made from stage 2 expiratory bulbospi nal neurons (E2Ns) in the caudal part of the ventral respiratory group in pentobarbitone-anesthetized cats, to characterize changes in neuro nal input resistance (R(n)) and synaptic inhibition occurring at the t ime of the expiratory-inspiratory phase transition of the respiratory cycle. 2. R(n) was maximal between 30-90% of stage 2 expiration, but d ecreased significantly during the last 10% of stage 2 expiration. Mean normalized R(n) for 60-90% of stage 2 expiration was 0.9 +/- 0.02, wh ile mean R(n) during the last 10% of stage 2 expiration was 0.68 +/- 0 .09 (n = 8). This decrease in R(n) began 200-300 ms before rapid hyper polarization of E2N membrane potential and onset of phrenic nerve acti vity. 3. Under conditions of strong central respiratory drive, constan t injection of positive current into E2Ns sometimes revealed a transie nt membrane hyperpolarization that straddled the expiratory-inspirator y phase transition. During this transient event, R(n) was markedly red uced. 4. Intracellular injection of Cl- or NO3- ions into E2Ns produce d reversal of chloride-dependent inhibitory synaptic potentials (IPSPs ). Comparison of averages of membrane potential pattern over the whole respiratory cycle during control conditions and IPSP reversal reveale d several periods of synaptic inhibition: 1)weak but progressively inc reasing synaptic inhibition during the second half of stage 2 expirati on, 2) strong transient synaptic inhibition beginning 200-300 ms befor e the onset of phrenic nerve activity and ending shortly after the ons et of phrenic nerve activity, and 3) strong but progressively decreasi ng synaptic inhibition throughout inspiration. Measurement of R(n) dur ing IPSP reversal showed that R(n) was most decreased during the inhib ition associated with expiratory-inspiratory phase transition. The tim e course of IPSP reversal and differences in the amount of negative cu rrent injection required to reverse the different periods of synaptic inhibition indicated that inhibitory inputs activated during stage 2 e xpiration may be located more proximal than those activated during ins piration. 5. Firing rate records taken from intra- or extracellular re cordings from early inspiratory (Early I) or pre-inspiratory (Pre I-al so called expiratory-inspiratory phase-spanning) neurons were used to generate cumulative cycle histograms of firing activity. Early I neuro ns (n = 16) usually fired their first action potential immediately bef ore phrenic nerve onset. Mean time between the first Early I discharge and phrenic nerve activity was 25 +/- 80 ms; only 2 Early I neurons f ired their first action potential > 100 ms before phrenic nerve. Pre I neurons (n = 6) began firing at low rates during the first half of st age 2 expiration, steadily increasing their firing rate through this p hase. A transient burst of firing activity in Pre I neurons occurred a round the expiratory-inspiratory phase transition, with peak firing re ached at times from 200 ms before to 100 ms after the onset of phrenic nerve activity. Pre I neurons then fired at declining rates through i nspiration. 6. The time course and relative strength of synaptic inhib ition in E2Ns was estimated by the relative difference between whole c ycles averages of membrane potential during control conditions and IPS P reversal. Synaptic inhibition increased slowly throughout stage 2 ex piration, showed a further rapid increase 200-300 ms before onset of p hrenic nerve activity, and then declined steadily throughout inspirati on. The possible effects of firing activity of Early I and Pre I neuro ns was assessed by calculation of average firing activity for each neu ron type throughout the respiratory cycle, using equal numbers of each neuron type. These two averages were then summed and compared with th e estimated synaptic inhibition observed in E2Ns. Summed Pre I and Ear ly I firing activity corresponded well with the time course of synapti c inhibition during stage 2 expiration, but not as well with synaptic inhibition during inspiration. 7. In conclusion, stage 2 expiratory bu lbospinal neurons receive previously undescribed synaptic inhibition d uring the later part of stage 2 expiration, which rapidly increases in strength 200-300 ms before the onset of phrenic nerve activity. The t ime course and strength of this inhibition corresponds well with firin g activity in pre-inspiratory neurons. This inhibition may occur at re latively proximal neuronal sites and could potentially play a signific ant role in controlling E2N firing rate and expiratory termination. Ho wever, E2Ns also receive a declining pattern of synaptic inhibition du ring inspiration that presumptively arises from inputs from early insp iratory neurons. An overlap of stage 2 expiratory and inspiratory inhi bition occurs at the expiratory-inspiratory phase transition and may b e necessary to fully effect the termination of expiration.