RETROTRAPEZOID NUCLEUS GLUTAMATE INJECTIONS - LONG-TERM STIMULATION OF PHRENIC ACTIVITY

In chloralose-urethan anesthetized, paralyzed, vagotomized, glomectomi zed, and servo-ventilated cats we examined the effects of 10 nl of glu tamate (10 mM, 100 mM, and 1 M) injected unilaterally over 60 s into t he region of the retrotrapezoid nucleus (RTN). Seven 10 mM glutamate i njections produced no consistent effects on the amplitude of the integ rated phrenic nerve signal, respiratory cycle duration, or blood press ure. Ten 100 mM injections consistently increased integrated phrenic a mplitude significantly from a baseline average of 31 +/- 2% (SE) of ma ximum to a peak response average of 50 +/- 3% of maximum. This effect was long lasting (45.6 +/- 8.6 min). Blood pressure responses were var iable. Seven 1 M glutamate injections consistently decreased integrate d phrenic amplitude significantly from a baseline average for all inje ctions of 29 +/- 3% of maximum to a peak average of 20 +/- 5% of maxim um. Respiratory cycle duration and blood pressure responses were varia ble. Prior injection into the RTN of 10 nl of 100 mM kynurenic acid at tenuated the subsequent response of the integrated phrenic amplitude t o injection of 10 nl of glutamate at the same site. Comparison of glut amate (10 nl, 100 mM) injected over 60 s vs. 30 ms showed that the pro longed increase in phrenic activity was related to the longer-duration (60-s) injections and that RTN single units were stimulated for up to 5 min on average after the 60-s injection with one unit showing an in crease in firing rate over 40 min. After the 30-ms injection, integrat ed phrenic amplitude and RTN unit mean firing rate were increased for the first two breaths and at 5 min after the injection. We conclude th at glutamate injected into the RTN increases local single-unit firing rate and the amplitude of the integrated phrenic activity. Injections made over 60 s result in prolonged phrenic stimulation and, in some ca ses, in RTN single-unit firing rate.