The pedunculopontine nucleus (PPN) is involved in the generation and maintenance of the cortically activated states of waking and rapid eye movement (REM) sleep, forming part of the brainstem reticular activating system (RAS). The dorsal subcoeruleus nucleus (SubCD) is a descending target of the PPN involved in the generation of REM sleep, muscle atonia, and ponto-geniculo-occipital (PGO) waves. The PPN and SubCD receive glutamatergic afferents from other mesopontine nuclei, and glutamatergic input has been proposed to be involved in the generation of arousal states. Injections of specific glutamate (Glu) receptor agonists into the PPN of the rat increased waking or REM sleep, while injections into the SubCD induced a REM sleep-like state with muscle atonia. Whole-cell patch clamp recordings were performed on brainstem slices from 9 to 17 day-old rat pups to test the effects of glutamatergic input to the PPN and SubCD in vitro. This age range was selected because it spans the developmental decrease in REM sleep that occurs in the rat from birth to postnatal day 30. Pharmacological and electrical stimulation were used to measure glutamatergic responses of PPN and SubCD neurons. These studies revealed that (1) all cells in the PPN and SubCD are excited by the Glu receptor agonists N-methyl-D-aspartic acid (NMDA) and kainic acid (KA). (2) In the PPN, a developmental decrease in the contribution of the NMDA receptor and developmental increase in the contribution of the KA receptor was observed following local stimulation and agonist exposure in different cell types. (3) In the SubCD, no developmental changes were observed in the relative contribution of KA and NMDA receptors to the response following local stimulation. However, there was a developmental decrease in the half-width duration of evoked responses and a decrease in the response following agonist exposure. (4) PPN afferents contain presynaptic KA receptors located on axon terminals that function to decrease Glu release. (5) Glutamatergic inputs induce membrane oscillations in PPN and SubCD neurons, which may underlie the repetitive AP firing properties of these neurons. Together, these studies provide novel information about the role of glutamate in the reticular activating system.
|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 73/05, Dissertation Abstracts International|
|Keywords:||Arousal, Dorsal subcoeruleus nuclei, Glutamate, Pedunculopontine, Rapid eye movement sleep, Synaptic neurotransmission|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be