Propofol enhances facial stimulation-evoked responses in the cerebellar granule cell layer via NMDA receptor activation in mice in vivo

• Published in: European journal of pharmacology 2016-10, Vol.788, p.37-44
• Main Authors: Jin, Wen-Zhe, Liu, Heng, Wan, Peng, Chu, Chun-Ping, Qiu, De-Lai
• Format: Article
• Language: English
• Subjects: Animals; Cerebellar granule cell layer (GCL); Cerebellum - cytology; Cerebellum - drug effects; Cerebellum - metabolism; Cerebellum - physiology; Evoked Potentials - drug effects; Face; Field potential recording; GABAA receptor; Mice; Mice, Inbred ICR; NMDA receptor; Physical Stimulation; Propofol; Propofol - pharmacology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Sensory stimulation
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2016.05.027

We recently reported that propofol depressed facial stimulation-evoked gamma-aminobutyric acid (GABA) transmission at cerebellar molecular layer interneuron–Purkinje cell (PC) synapses in mice in vivo, but facilitated excitatory parallel fiber inputs onto PCs. Here, we examine the effects of propofol on cerebellar granule cell layer (GCL) responses to facial stimulation in urethane-anesthetized mice, using electrophysiological and pharmacological methods. Cerebellar surface perfusion of propofol (50–1000μM) facilitated field potentials evoked in the cerebellar GCL by air-puff stimulation of the ipsilateral whisker pad, shown by increases in the half-width and area under the curve (AUC) of the stimulus onset response (Ron). Propofol also significantly increased the amplitude of the stimulus offset response (Roff) and Roff/Ron ratio. The propofol-induced increase in Ron AUC was dose-dependent, with a 50% effective concentration (EC50) of 242.4µM. Application of the GABAA receptor antagonist gabazine (20μM) significantly increased the amplitude, half-width, rise tau and AUC of Ron, but these parameters were further increased by additional application of propofol (300µM). Notably, application of the N-methyl-d-aspartate (NMDA) receptor blocker D-APV (250µM) significantly attenuated the half-width and AUC of Ron and the amplitude of Roff, without significantly changing the amplitude of Ron. These results indicate that propofol enhanced facial stimulation-evoked responses in the cerebellar GCL via NMDA receptor activation, which resulted in the facilitation of excitatory parallel fiber inputs onto cerebellar PCs in mice in vivo.