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

• Published in: Frontiers in cellular neuroscience Vol. 4
• Main Authors: Coulon, Philippe, Kanyshkova, Tatyana, Broicher, Tilman, Munsch, Thomas, Wettschureck, Nina, Seidenbecher, Thomas, Meuth, Sven G., Offermanns, Stefan, Pape, Hans-Christian, Budde, Thomas
• Format: Journal Article
• Language: English
• Published: Lausanne Frontiers Research Foundation 25-10-2010; Frontiers Media S.A
• Subjects: Acetylcholine receptors (muscarinic); Brain stem; Cerebral cortex; Fibers; G protein-coupled receptors; G-protein; gene knock out; Glutamatergic transmission; Glutamic acid receptors (metabotropic); Lateral geniculate nucleus; metabotropic glutamate receptor; muscarinic receptor; Neuroscience; Neurotransmitters; Proteins; Serotonin; serotonin receptor; Sleep; thalamic function; Thalamus; United States > US; Germany
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2010.00132

In thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional Gαq knock out on the background of a constitutive Gα11 knock out (Gαq/Gα11 -/-) 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 depolarisation of Vrest which was sufficient to suppress burst firing. This depolarisation was concentration-dependent (100 μM: +6 ± 1 mV, n = 10; 200 μM: +10 ± 1 mV, n = 7) and had a conditioning effect on the activation of other Gαq-mediated pathways. The depolarisation was significantly reduced in Gαq</sub/Gα11</sub -/- (100 μM: 3 ± 1 mV, n = 11; 200 μM: 5 ± 1 mV, n = 6) and was apparently insufficient to suppress burst firing. Activating Gαq coupled muscarinic receptors affected the magnitude of α-m-5-HT induced effects in a reciprocal manner. Furthermore, the depolarising effect of mGluR1 agonists was significantly reduced in Gαq/Gα11 -/- mice. Immunohistochemical stainings revealed binding of 5-HT2CR- and mGluR1α-, but not of 5-HT2AR-specific antibodies in the dLGN of Gαq/Gα11 -/- mice. In conclusion, these findings demonstrate that transmitters of ascending brainstem fibres and corticofugal fibres both signal via a central element in the form of Gq/G11-mediated pathways to control activity modes in the thalamocortical system.