1. The actions of acetylcholine (ACh) on the GABAergic neurons of the perigeniculate nucleus (PGN) were investigated with the use of extra- and intracellular recording techniques in spontaneously spindling ferret thalamic slices maintained in vitro. 2. Local application of ACh to PGN neurons resulted in rapid depolarization followed by a longer lasting hyperpolarization. Neither of these responses were abolished by blockade of synaptic transmission with tetrodotoxin (TTX) nor with low Ca2+ and elevated Mg2+ solution, indicating that they are direct postsynaptic actions of ACh on PGN cells. Functionally, the rapid depolarizing response could activate both single spike activity, as well as low-threshold Ca2+ spike mediated bursts. 3. The fast depolarizing response to ACh was selectively blocked by application of the nicotinic antagonist hexamethonium, whereas the slow hyperpolarizing response to ACh was selectively blocked by application of the muscarinic antagonist (-)scopolamine. Application of both hexamethonium and (-)scopolamine blocked the modulation of PGN action- potential firing by ACh. 4. Local application of the nicotinic agonist 1,1- dimethyl-4-phenylpiperazinium (DMPP) resulted in a depolarizing response and an increase in membrane conductance, whereas application of the muscarinic agonist DL-muscarine chloride resulted in a hyperpolarizing response and an increase in membrane conductance. When applied to spontaneously spindling PGN cells, both DMPP and DL-muscarine blocked the occurrence of spindle oscillations. However, only DMPP was associated with depolarization and the generation of single spike activity. 5. These results indicate that the GABAergic cells of the PGN possess postsynaptic nicotinic as well as muscarinic receptors. Activation of the nicotinic receptors results in rapid depolarization of these neurons and can activate both single spike and burst activity. These responses may be important in the generation of pontogeniculo-occipital (PGO) waves and membrane depolarizations during rapid-eye-movement (REM) sleep and arousal.
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