The Pedunculopontine nucleus (PPN) is thought to be critical for switching from slow wave sleep (SWS) to waking and rapid eye movement (REM) sleep via its cholinergic innervation of the thalamus. The Parafascicular nucleus (Pt), a "non-specific" thalamocortical nucleus, is one of the major targets of the PPN. This dissertation employed retrograde labeling and whole-cell patch clamp recording techniques in rat brain slices to investigate the cholinergic modulation of gabaergic, glutamatergic and electrical synaptic transmission in PPN thalamic-projecting neurons, as well as the post-synaptic responses of output PPN neurons and Pf cells to the administration of cholinergic agents. This project determined that (1) Post-synaptic cholinergic responses of Pf neurons showed a transition from mixed excitatory (via M1 and nicotinic receptors) and inhibitory (via M2 receptors), to predominantly inhibitory, responses during the developmental decrease in REM sleep; (2) Pf neurons exhibiting different cholinergic responses had distinct membrane properties, which also changed during development; (3) Both cholinergic and non-cholinergic PPN neurons send efferent projections to the thalamus; (4) The non-selective cholinergic receptor agonist, carbachol, predominantly enhanced inhibitory and excitatory fast synaptic transmission in PPN output neurons, mainly through activation of M1 and/or nicotinic cholinergic receptors located on the soma or axons of pre-synaptic gabaergic and glutamatergic neurons; (5) Electrical coupling, which regulates rhythmic membrane oscillations, can be present in PPN output neurons, and these neurons showed different post-synaptic cholinergic responses; (6) PPN output neurons were mainly inhibited by carbachol due to activation of M2 and probably M4 receptors as well, whereas, a few PPN output cells also exhibited excitatory (via M1 and nicotinic receptors) or biphasic responses. These studies provided some important advances in the understanding of the mechanisms involved in the modulation of cortical arousal states at the level of subcortical networks.
|School:||University of Arkansas for Medical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 70/04, Dissertation Abstracts International|
|Keywords:||Cholinergic modulation, Cortical arousal, Electrical coupling, Fast synaptic transmission, Parafascicular nucleus, Pedunculopontine nucleus|
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