Developmental changes in the effects of serotonin on neurons in the region of the pedunculopontine nucleus

Abstract

The percent of rapid eye movement (REM) sleep decreases dramatically between 10 and 30 days postnatally in the rat. The pedunculopontine nucleus (PPN) is known to modulate waking and REM sleep. We recorded intracellularly from 127 neurons in the PPN in 12–21-day rat brainstem slices maintained in warmed, oxygenated artificial cerebrospinal fluid. We identified three types of PPN neurons based on intrinsic membrane properties, type I (LTS), type II (A) and type III (A+LTS), as previously described. The percent of type I neurons increased from 6% at 12 days to 17% by 21 days, while the percent of type III neurons decreased from 21% at 12–17 days, to 4% after 17 days. Thus, PPN neurons may differentiate into type I bursting neurons and type II slow-firing neurons across this critical stage in development. The 5-HT1 receptor agonist 5-carboxyamido-tryptamine (5-CT) was found to hyperpolarize 58% of 12–16-day PPN neurons, did not affect 25% and depolarized 17%. However, a higher percentage of 17–21-day PPN neurons were hyperpolarized (85%), and a lower percentage unaffected (10%) or depolarized (5%), suggesting that serotonergic responses switched from both excitatory and inhibitory before, to almost purely inhibitory after, 17 days. These findings indicate a reorganization of PPN intrinsic membrane properties and serotonergic responses occur across this stage, in keeping with the proposed presence of a REM sleep inhibitory process during development. We suggest that disturbances in this developmental process may lead to disorders marked by increased REM sleep drive.