Abstract 17915: Brainstem Neuronal Networks for Breathing Control Involve a Disinhibitory Projection From the Dorsal Medulla

The critical neuronal networks for breathing control known to be located in the brainstem are still not fully understood. γ-Aminobutyric acid (GABA) is a neurotransmitter that not only plays an important role in the networks, but also allows investigational interventions to the networks. To gain a fast, local and reversible access to brainstem GABAergic neurons, we developed a strain of transgenic mice that expressed channelrhodopsin in a tandem with eYFP in GABAergic neurons directed by the glutamic acid decarboxylase 2 promotor, the Gad2-ChR mouse. We firstly studied eYFP fluorescence in brainstem tissue sections. Several groups of previously known GABAergic neurons were positively labelled. Breathing response to optostimulation and CO 2 challenge were then studied in the anesthetized mice in vivo . When the optostimulation was applied to the ventral surface of the brainstem, especially the medulla, phrenic nerve activity was remarkably inhibited. Surprisingly, we found that optostimulation to the dorsal surface of the brainstem induced significant augmentation of both breathing activity and CO 2 chemosensitivity in the Gad2-ChR mice. Both breathing frequency and integrated phrenic amplitude were augmented. The effect was reversible and fast reaching peaking activation within 1 min. With respect to ventilation responses, optostimulation was nearly as potent as the response to 6% CO 2 . In the presence of 6% CO 2 , optostimulation was still capable of enhancing breathing activity. The breathing stimulation effect of optical GABA activation was located to the medulla. These observations suggest that respiratory neuronal networks involve a disinhibitory projection from dorsal GABAergic neurons in the medulla to a group of unidentified inhibitory neurons that are actively inhibit central breathing activity.