The pedunculopontine nucleus (PPN) is part of the brainstem reticular activating system (RAS), and is active during waking and REM sleep. Previous studies showed that all PPN neurons tested fired at gamma frequencies when depolarized using current ramps. Further investigation showed that this intrinsic membrane property is mediated by high-threshold N- and P/Q- type Ca 2+ channels. We perfomed in vitro patch-clamp recordings on PPN neurons from Sprague-Dawley rat pups aged 10 to 16 days old, and applied current ramps to induce membrane oscillations. The present sudy investigated the intracellular mechanisms modulating gamma band activity in the PPN. Results revealed three independent popoulations of PPN neurons that can generate gamma band oscillations. Cells with only N-type Ca 2+ channels (30%), only P/Q-type Ca2+ channels (20%), or both N- and P/Q-type Ca2+ channels (50%). Further results showed that PPN neurons generated gamma activity through the cAMP/PKA and CaMKII pathways. We found that oscillations in cells with only N-type Ca 2+ channels were mediated by the cAMP/PKA pathway (presumed “REM-on” neurons). Oscillations in cells with only P/Q-type Ca2+ channels were mediated by the CaMKII pathway (presumed “Wake-on” neurons). Lastly, oscillations in cells with both N- and P/Q-type Ca2+ channels were mediated by the cAMP/PKA and CaMKII pathways (presumed “Wake/REM-on neurons). Taken together, these studies provided insights showing that PPN gamma oscillations are modulated by two independent pathways related to the expression of different Ca2+ channel subtypes.
|Commitee:||Hayar, Abdallah, Mennemeier, Mark, Messias, Erick, Skinner, Robert|
|School:||University of Arkansas for Medical Sciences|
|Department:||Neurobiology and Developmental Science|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 77/11(E), Dissertation Abstracts International|
|Keywords:||Arousal, Calcium channels, Gamma, PPN, Sleep|
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