δ-Subunit Containing GABA Receptors Modulate Respiratory Networks.

Persistent and stable respiratory activity across behavioral states is key to homeostasis. Extrasynaptic δ-subunit containing GABA receptors (δGABARs) mediate tonic inhibition and regulate network activity. However, the influence of δGABARs on respiratory rhythm and motor outputs is unknown. We manipulated extra-synaptic GABA receptor function in the preBötzinger Complex (preBötC), a site central to the generation of inspiratory motor activity in mammals. Activation of preBötC δGABARs in anesthetized rats and wild-type mice decreased breathing rate. In δGABAR knockout (Gabrd ) mice, however, δGABARs activation had no effect on breathing rate. We then found that during active wakefulness associated with behaviors and movements, diaphragm activation was higher in the Gabrd compared to wild-type mice, but not in other states. These findings identify that δGABARs modulate the respiratory network, which is critical to understand how δGABARs change breathing in pathological conditions affecting extra-synaptic GABA receptor function such as exposure to anesthetics and neurosteroids.