Endogenous Glutamatergic Control of Rhythmically Active Mammalian Respiratory Motoneurons In Vivo

Abstract

The transmission of rhythmic drive to respiratory motoneurons in vitro is critically dependent on glutamate acting primarily on non-NMDA receptors. We determined whether both non-NMDA and NMDA receptors contribute to respiratory drive transmission at respiratory motoneurons in the intact organism, both in the state of anesthesia and in the same animals during natural behaviors. Twentyseven rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states and genioglossus and diaphragm electrodes for respiratory muscle recordings. Microdialysis probes were inserted into the hypoglossal motor nucleus (HMN). Under anesthesia, non-NMDA or NMDA receptor antagonism significantly decreased respiratory-related genioglossus activity, indicating a contribution of each receptor to respiratory drive transmission at the HMN. However, despite the presence of respiratory-related genioglossus activity in the same rats across sleep-wake states, neither non-NMDA receptor antagonism at the HMN nor glutamate uptake inhibition had any effect on respiratory-related genioglossus activity. These results showed that, compared with anesthesia, respiratory drive transmission through the non-NMDA receptor is low in the behaving organism. In contrast, glutamate uptake inhibition increased tonic genioglossus activity in wakefulness and non-rapid-eye-movement sleep, indicating a functional endogenous glutamatergic modulation of tonic, but not respiratory, motor tone. Such an effect on tonic drive may contribute to the suppression of both tonic and respiratory-related genioglossus activity in wakefulness and sleep with NMDA receptor antagonism at the HMN. These data do not refute previous identification of a glutamatergic (mostly non-NMDA receptor activating) respiratory drive to hypoglossal motoneurons, but this mechanism is more prominent in anesthetized or in vitro preparations.

5-HT1AReceptor-Responsive Pedunculopontine Tegmental Neurons Suppress REM Sleep and Respiratory Motor Activity

“…Mean neck muscle activity, diaphragm amplitude and respiratory rate were also calculated in the same consecutive 5 s time-bins for all the periods of sleep and wakefulness in each rat. One rat was excluded from the analysis of genioglossus muscle activity as no respiratory-related activity was recorded under any circumstances during the experiment, which is highly atypical of the rats in this and other studies from our laboratory (Sood et al, 2005;Chan et al, 2006;Younes et al, 2007;Steenland et al, 2008), and as such was a possible indicator that the electrodes were in a different tongue muscle in that animal. In addition, in the potential event of there being little effect of 8-OH-DPAT on the amplitude of respiratory-related genioglossus, such a minimal effect could not be reliably attributed to a lack of drug effect per se and may simply have been due to the fact that there was little/no signal to suppress.…”

“…A surgical plane of anesthesia, as judged by abolition of the pedal withdrawal and corneal blink reflexes, was maintained with isoflurane (2-2.5%) administered with an anesthesia mask placed over the snout. The rats were then implanted with EEG and neck EMG electrodes for the determination of sleep-wake states, and with genioglossus and diaphragm electrodes for respiratory muscle recording (Steenland et al, 2008). Genioglossus muscle electrodes were considered correctly positioned if their electrical stimulation produced apical tongue contraction.…”

State-dependent vs. central motor effects of ethanol on breathing

“…Respiratory muscle activities were quantified as previously described (22,57). The EMG signals were analyzed from the respective moving-time average signals (above electrical zero).…”

“…The EEG was sampled by computer at 500 Hz and then analyzed on overlapping segments of 1,024 samples, windowed using a raised cosine (Hamming) function, and subjected to a fast Fourier transform to yield the power spectrum (22,57). The window was advanced in steps of 512 samples, and the mean power spectrum of the EEG signal for each 5-s epoch was calculated.…”

Dopamine triggers skeletal muscle tone by activating D1-like receptors on somatic motoneurons

“…2, E and F). Because a glutamatergic mechanism relays inspiratory drive onto respiratory motoneurons (Funk et al 1993;Steenland et al 2006Steenland et al , 2008Zuperku et al 2008), dopamine should presumably amplify this drive. However, since inspiratory activity remained unaffected, we conclude that dopamine primarily activates trigeminal motoneurons by a D 1 -like receptor mechanism.…”