AUTHOR=Coulon Philippe , Kanyshkova Tatyana , Broicher Tilman , Munsch Thomas , Wettschureck Nina , Seidenbecher Thomas , Meuth Sven G., Offermanns Stefan , Pape Hans-Christian , Budde Thomas 

TITLE=Activity Modes in Thalamocortical Relay Neurons are Modulated by Gq/G11 Family G-proteins – Serotonergic and Glutamatergic Signaling

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=4

YEAR=2010

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2010.00132

DOI=10.3389/fncel.2010.00132

ISSN=1662-5102

ABSTRACT=<p>In thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional Gα<sub>q</sub> knockout on the background of a constitutive Gα<sub>11</sub> knockout (Gα<sub>q</sub>/Gα<sub>11</sub><sup>−/−</sup>) was used to determine the contribution of Gq/G11 family G-proteins to metabotropic serotonin (5-HT) and glutamate (Glu) function in the dorsal part of the lateral geniculate nucleus (dLGN). In control mice, current clamp recordings showed that α-m-5-HT induced a depolarization of V<sub>rest</sub> which was sufficient to suppress burst firing. This depolarization was concentration-dependent (100 μM: +6 ± 1 mV, <italic>n</italic> = 10; 200 μM: +10 ± 1 mV, <italic>n</italic> = 7) and had a conditioning effect on the activation of other Gα<sub>q</sub>-mediated pathways. The depolarization was significantly reduced in Gα<sub>q</sub>/Gα<sub>11</sub><sup>−/−</sup> (100 μM: 3 ± 1 mV, <italic>n</italic> = 11; 200 μM: 5 ± 1 mV, <italic>n</italic> = 6) and was apparently insufficient to suppress burst firing. Activating Gα<sub>q</sub>-coupled muscarinic receptors affected the magnitude of α-m-5-HT-induced effects in a reciprocal manner. Furthermore, the depolarizing effect of mGluR1 agonists was significantly reduced in Gα<sub>q</sub>/Gα<sub>11</sub><sup>−/−</sup> mice. Immunohistochemical stainings revealed binding of 5-HT<sub>2C</sub>R- and mGluR1α-, but not of 5-HT<sub>2A</sub>R-specific antibodies in the dLGN of Gα<sub>q</sub>/Gα<sub>11</sub><sup>−/−</sup> mice. In conclusion, these findings demonstrate that transmitters of ascending brainstem fibers and corticofugal fibers both signal via a central element in the form of Gq/G11-mediated pathways to control activity modes in the TC system.</p>