δ-Subunit Containing GABAA Receptors Modulate Respiratory Networks

作者：Montandon, Gaspard^*; Wu, Haiying; Liu, Hattie; Vu, Michael T.; Orser, Beverley A.; Horner, Richard L.

来源：Scientific Reports, 2017, 7(1): 18105.

DOI：10.1038/s41598-017-17379-x

• PRE-BOTZINGER COMPLEX
• INHIBITION
• NEURONS
• RHYTHM
• SENSITIVITY
• CHANNELS
• MEDIATE

Persistent and stable respiratory activity across behavioral states is key to homeostasis. Extrasynaptic delta-subunit containing GABA(A) receptors (delta GABA(A)Rs) mediate tonic inhibition and regulate network activity. However, the influence of dGABAARs on respiratory rhythm and motor outputs is unknown. We manipulated extra-synaptic GABAA receptor function in the preBotzinger Complex (preBotC), a site central to the generation of inspiratory motor activity in mammals. Activation of preBotC dGABA(A)Rs in anesthetized rats and wild-type mice decreased breathing rate. In delta GABA(A)R knockout (Gabrd(-/-)) mice, however, dGABAARs 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 dGABAARs modulate the respiratory network, which is critical to understand how dGABAARs change breathing in pathological conditions affecting extra-synaptic GABAA receptor function such as exposure to anesthetics and neurosteroids.

• 出版日期2017-12-22
• 单位昆明医科大学