MODULATION OF SPINDLE OSCILLATIONS BY ACETYLCHOLINE, CHOLECYSTOKININ AND 1S,3R-ACPD IN THE FERRET LATERAL GENICULATE AND PERIGENICULATE NUCLEI IN-VITRO

The transition from sleep to waking is associated with the abolition o f spindle waves and the appearance of tonic activity in thalamocortica l neurons and thalamic reticular/perigeniculate GABAergic cells. We te sted the possibility that changes such as these may arise through modu lation of the leak potassium current, I-KL, by examining the effects o f neurotransmitters known to modulate this current on spindle wave gen eration in the ferret geniculate slice maintained in vitro. Local appl ication of agents that reduce I-KL in thalamocortical neurons, includi ng acetylcholine, DL-muscarine chloride and the glutamate metabotropic receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD), to spontaneously spindling thalamocortical neurons resulted in a 5-10 mV membrane depolarization and the abolition of spindle wave s. Local application of 1S,3R-ACPD and cholecystokinin-8-sulfate, both of which reduce I-KL, to GABAergic neurons of the perigeniculate nucl eus resulted in a 10-20 mV membrane depolarization, appearance of toni c discharge and the abolition of spindle wave generation. Local applic ation of 1S,3R-ACPD and cholecystokinin to the perigeniculate nucleus while recording from thalamocortical neurons resulted in the abolition of spindle wave-associated inhibitory postsynaptic potentials and the occurrence of a continuous barrage of smaller amplitude inhibitory po stsynaptic potentials, presumably in response to depolarization and to nic discharge of perigeniculate neurons. These results indicate that m odulation of I-KL in thalamocortical neurons and perigeniculate neuron s is capable of abolishing the generation of spindle waves in thalamic networks. Through the modulation of I-KL, ascending and descending ac tivating systems may control the state of the thalamus such that the t ransition from slow wave sleep to waking is associated with the abolit ion of slow, synchronized rhythms and the facilitation of a stale that is conducive to sensory receptor field analysis, arousal and percepti on. (C) 1997 IBRO.