Expression of ethanol sensitive glycine receptors in several brain regions

Seminar | June 25 | 2-3:30 p.m. | 125 Li Ka Shing Center

 Luis Aguayo, University of Concepcion, Chile

 Neuroscience Institute, Helen Wills

Synaptic glycine receptors (GlyR) are expressed primarily in spinal cord and brain stem neurons. GlyRs are sensitive to general anesthetics, neurosteroids, Zn2+ and ethanol. Recently, GlyRs were also found in other supratentorial regions, but their properties are largely unknown. Mesolimbic regions, such as ventral tegmental area (VTA) and nucleus accumbens (nAc), were also found to express GlyRs of a still unidentified molecular nature. This information is of interest because these areas might be important for the rewarding effects of drugs of abuse. The aim of this work was to identify the presence of GlyRs in regions of the reward system (prefrontal cortex, PFC, nAc and VTA) and to characterize electrophysiological properties and sensitivity to ethanol in WT and alpha1 KI mice.

We detected the GlyR α1 subunit in PFC, VTA and nAc in C57BL/6J mice. Further analysis suggests the presence of both synaptic and non-synaptic GlyRs in the three areas. Recordings from acutely dissociated neurons showed that most neurons displayed a large current (>500 pA at 1 mM of glycine). Data showed that the currents had different sensitivities in the three cell types. Interestingly in WT mice, VTA and nAc neurons were potentiated by ethanol whereas PFC neurons were insensitive. VTA and nAc neurons in KI mice were less affected by ethanol supporting the idea that these brain regions express α1 subunits. The results suggest that the receptor conformation and sensitivity to glycine and ethanol are different in distinct brain areas.