Activity Modes in Thalamocortical Relay Neurons are Modulated by G(q)/G(11) 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 Gα(q) knockout on the background of a constitutive Gα(11) knockout (Gα(q)/Gα(11) (-/-)) 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(rest) which was sufficient to suppress burst firing. This depolarization 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 Gα(q)-mediated pathways. The depolarization was significantly reduced in Gα(q)/Gα(11) (-/-) (100 μM: 3 ± 1 mV, n = 11; 200 μM: 5 ± 1 mV, n = 6) and was apparently insufficient to suppress burst firing. Activating Gα(q)-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(q)/Gα(11) (-/-) mice. Immunohistochemical stainings revealed binding of 5-HT(2C)R- and mGluR1α-, but not of 5-HT(2A)R-specific antibodies in the dLGN of Gα(q)/Gα(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 Gq/G11-mediated pathways to control activity modes in the TC system.
Institut für Physiologie I, Westfälische Wilhelms-Universität Münster Münster, Germany.
Philippe
P
Coulon
Tatyana
T
Kanyshkova
Tilman
T
Broicher
Thomas
T
Munsch
Nina
N
Wettschureck
Thomas
T
Seidenbecher
Sven G
SG
Meuth
Stefan
S
Offermanns
Hans-Christian
HC
Pape
Thomas
T
Budde
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