Modulation of spindle oscillations by acetylcholine, cholecystokinin and 1S,3R-ACPD in the ferret lateral geniculate and perigeniculate nuclei in vitro

Neuroscience. 1997 Mar;77(2):335-50. doi: 10.1016/s0306-4522(96)00481-2.


The transition from sleep to waking is associated with the abolition of spindle waves and the appearance of tonic activity in thalamocortical neurons and thalamic reticular/perigeniculate GABAergic cells. We tested the possibility that changes such as these may arise through modulation of the leak potassium current, IKL, by examining the effects of neurotransmitters known to modulate this current on spindle wave generation in the ferret geniculate slice maintained in vitro. Local application of agents that reduce IKL in thalamocortical neurons, including 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 waves. Local application of 1S,3R-ACPD and cholecystokinin-8-sulfate, both of which reduce IKL, to GABAergic neurons of the perigeniculate nucleus resulted in a 10-20 mV membrane depolarization, appearance of tonic discharge and the abolition of spindle wave generation. Local application 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 postsynaptic potentials, presumably in response to depolarization and tonic discharge of perigeniculate neurons. These results indicate that modulation of IKL in thalamocortical neurons and perigeniculate neurons is capable of abolishing the generation of spindle waves in thalamic networks. Through the modulation of IKL, ascending and descending activating systems may control the state of the thalamus such that the transition from slow wave sleep to waking is associated with the abolition of slow, synchronized rhythms and the facilitation of a state that is conducive to sensory receptor field analysis, arousal and perception.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology
  • Cholecystokinin / pharmacology*
  • Cycloleucine / analogs & derivatives*
  • Cycloleucine / pharmacology
  • Electrophysiology
  • Extracellular Space / physiology
  • Female
  • Ferrets / physiology*
  • Geniculate Bodies / drug effects*
  • In Vitro Techniques
  • Male
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / physiology
  • Thalamus / cytology
  • Thalamus / physiology
  • gamma-Aminobutyric Acid / physiology


  • Neuroprotective Agents
  • Potassium Channels
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • gamma-Aminobutyric Acid
  • Cholecystokinin
  • Acetylcholine