The pedunculopontine nucleus (PPN) is part of the brainstem Reticular Activating System (RAS), and is active during waking and REM sleep. The PPN sends ascending cholinergic projections to the intralaminar thalamus, especially the parafascicular nucleus (Pf). The Pf nucleus is part of the "non-specific" thalamocortical system that sends the widespread projections throughout the cortex, and is thought to play a significant role in maintaining consciousness and selective attention. Electrical stimulation of either the PPN or centrolateral (Cl)-Pf nuclei in vivo is known to produce arousal and gamma band activity in the cortical EEG. High threshold P/Q-type channels are known to be located in the dendrites of "specific" TC neurons and support gamma band oscillations in the thalamus, as well as at cortical levels. Whole-cell patch clamp recordings were performed on brainstem slices from 9 to 25 day-old rat pups to test the role of high-threshold calcium channels in generating the gamma band activity in PPN and Pf nuclei in vitro. This age range was selected because it spans the developmental decrease in rapid eye movement (REM) sleep that occurs in the rat from birth to postnatal day 30. The presence of high-threshold voltage-sensitive calcium channels in these nuclei was pharmacologically determined. These studies revealed that 1) all cells in the PPN have the ability to oscillate at gamma band frequency via P/Q and N-type calcium channels; 2) This activity can be modified by the nonspecific cholinergic agonist carbachol (CAR); 3) PPN population studies revealed that CAR induced local field potentials were also high-threshold calcium channel-dependent; 4) In the Pf, a developmental increase in the frequency of oscillations plateaus at gamma band; 5) P/Q and N-type calcium channels generate this activity in the Pf as well, which can also be modified by CAR; and 6) Local field potential studies in the Pf showed that CAR-induced oscillations were also high-threshold calcium channel-dependent. Together these studies provide novel information about the role of high-threshold calcium channels in nuclei of the RAS involved in sleep-wake regulation and awareness.
|Commitee:||Al-Chaer, Elie, Childs, Gwen, Hayar, Abdallah, Skinner, Robert|
|School:||University of Arkansas for Medical Sciences|
|Department:||Neurobiology and Developmental Science|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 73/11(E), Dissertation Abstracts International|
|Keywords:||Arousal, Gamma oscillations, Parafascicular neurons, Pedunculopontine|
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