Muscarinic ACh receptor-mediated control of thalamic activity via Gq/G11-family G-proteins

A genetic knock out was used to determine the specific contribution of G(q)/G(11)-family G-proteins to the function of thalamocortical relay (TC) neurons. Disruption of G alpha(q) function in a conditional forebrain-specific G alpha(q)/Ga-11-double-deficient mouse line (G alpha(q)/G alpha(-/-)(11)) had no effects on the resting membrane potential (V-rest) and the amplitude of the standing outward current (I-SO). Stimulation of muscarinic acetylcholine (ACh) receptors (mAChR; muscarine, 50 mu M) induced a decrease in ISO amplitude in wild-type mice (36 +/- 4%, n=5), a constitutive G alpha(11)-deficient mouse line (G alpha(-/-)(11); 36 +/- 3%, n=8), and G alpha(q)/G alpha(-/-)(11) (11 +/- 2%, n=16). Current-clamp recordings revealed a muscarine-induced positive shift in V-rest of 23 +/- 2 mV (n=6), 18 +/- 5 mV (n=5), and 2 +/- 1 mV (n=9) in wild type, G alpha(-/-)(11), and G alpha(q)/G alpha(-/)(11), respectively. This depolarization was associated with a change in TC neuron activity from burst to tonic firing in wild type and G alpha(-/-)(11), but not in G alpha(q)/G alpha(-/-)(11) . The use of specific antibodies and of pharmacological agents with preferred affinity points to the contribution of m(1)AChR and m(3)AChR. In conclusion, we present two novel aspects of the physiology of the thalamocortical system by demonstrating that the depolarization of TC neurons, which is induced by the action of transmitters of ascending brainstem fibers, is governed roughly equally by both m(1)AChR and m(3)AChR and is transduced by G alpha(q) but not by G alpha(11).