Activity modes in thalamocortical relay neurons are modulated by Gq/G11 family G-proteins - serotonergic and glutamatergic signaling

In thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional G alpha(q) knockout on the background of a constitutive G alpha(11) knockout (G alpha(q)/G alpha(-/-)(11)) was used to determine the contribution of G(q)/G(11) 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 alpha-m-5-HT induced a depolarization of V-rest which was sufficient to suppress burst firing. This depolarization was concentration-dependent (100 mu M: +6+/-1 mV, n = 10; 200 mu M: + 10+/-1 mV, n = 7) and had a conditioning effect on the activation of other G alpha(q)-mediated pathways. The depolarization was significantly reduced in G alpha(q)/G alpha(-/-)(11)(100 mu M: 3+/-1 mV, n = 11; 200 mu M: 5+/-1 mV, n = 6) and was apparently insufficient to suppress burst firing. Activating G alpha(q)-coupled muscarinic receptors affected the magnitude of alpha-m-5-HT-induced effects in a reciprocal manner. Furthermore, the depolarizing effect of mGluR1 agonists was significantly reduced in G alpha(q)/G alpha(-/-)(11) mice. Immunohistochemical stainings revealed binding of 5-HT2CR-and mGluR1 alpha-, but not of 5-HT2AR-specific antibodies in the dLGN of G alpha(q)/G alpha(-/-)(11) 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 G(q)/G(11)-mediated pathways to control activity modes in the TC system.