Responses of Developing Pedunculopontine Neurons to Glutamate Receptor Agonists 1

27 The pedunculopontine nucleus (PPN) is involved in the generation and maintenance of 28 waking and rapid eye movement (REM) sleep, forming part of the reticular activating system. 29 The PPN receives glutamatergic afferents from other mesopontine nuclei and glutamatergic 30 input is believed to be involved in the generation of arousal states. We tested the hypothesis 31 that, from postnatal days 9 to 17 in the rat, there are developmental changes in the glutamate 32 receptor subtypes that contribute to the responses of PPN neurons. Whole-cell patch clamp 33 recordings were conducted using brainstem slices from 9-17 days old rats. All cells (type I, II, 34 and III; randomly selected or thalamic-projecting) responded to bath application of the glutamate 35 receptor agonists N-methyl-D-aspartic acid (NMDA) and kainic acid (KA). A developmental 36 decrease in the contribution of the NMDA receptor and developmental increase in the 37 contribution of the KA receptor was observed following electrical stimulation-induced glutamate 38 input. These changes were also observed following bath application in different cell types 39 (randomly selected vs. thalamic-projecting). KA bath application produced an increase in the 40 paired-pulse ratio (PPR) and a decrease in the frequency of miniature EPSCs (mEPSCs), 41 suggesting that presynaptic kainate autoreceptors may decrease the probability of synaptic 42 glutamate input. In contrast, NMDA application produced no changes in the PPR or mEPSCs. 43 Changes in glutamatergic excitability of PPN cell types could underlie the developmental 44 decrease in REM sleep. 45 46 47 48