Brain Research, 458 (1988) 285-302 285 Elsevier BRE 13876 Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. II. Effects upon sleep-waking states Harry H. Webster and Barbara E. Jones Departments of Psychology, Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QuL (Canada) (Accepted 22 March 1988) Key words: Choline acetyltransferase; Tyrosine hydroxylase; Reticular formation; Paradoxical sleep; Wakefulness Kainic acid was injected bilaterally (4.8/~g in 1.2/A each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy the cholinergic neurons located in that region and thus to study the effects of their destruction upon sleep-waking states. The kainic acid produced a large area of nerve cell loss and/or gliosis centered in the dorsolateral tegmentum-cholinergic cell area, that includes the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei rostrally (A1-P2), and the parabrachi- al (PB) and locus coeruleus (LC) nuclei caudally (P3-P5). The mean loss of choline acetyltransferase (ChAT)-immunoreactive neu- rons within this area was 60% with a range from 25 % to 85% across 11 cats. The mean loss of tyrosine hydroxylase (TH)-immunoreac- tive neurons, differentially distributed through the same region, was 35% with a range of 0-50%. Whereas the kainic acid lesions ap- peared to have only slight effects upon wakefulness and slow-wave sleep, they had marked effects upon paradoxical sleep (PS), which varied in degree across animals. In cats with the most extensive destruction of cholinergic neurons, PS was eliminated in the first few weeks following the lesion and then reappeared as isolated episodes characterized by sparse, low amplitude PGO spikes in association with few eye movements and an activated cortex, though in absence of neck muscle atonia. Although these PS-like episodes varied in amount, they were significantly less than baseline PS in percent and in duration for the group of 11 animals over one month recording. The PGO spike rate was significantly reduced; the EMG amplitude was significantly increased, marking a loss of neck muscle atonia. The percent of PS-like epochs, the rate of PGO spiking and the EMG amplitude on postlesion day 28 were found to be significantly correlated with the volume of the lesion within the dorsolateral pontine tegmentum-cholinergic cell area. The percent PS-like epi- sodes and PGO spike rate were significantly correlated with the number of remaining ChAT-immunoreactive neurons, but not with the number of remaining TH-immunoreactive neurons within this region. These results suggest that cholinergic pontomesencephalic neurons may be critically involved in the generation of paradoxical sleep and its phasic events. INTRODUCTION The pontomesencephalic tegmentum has been known for many years to contain neuronal elements that are critically important for the generation and maintenance of sleep-waking states 52. From the clas- sical studies of Moruzzi and Magoun 53, neurons lo- cated in the oral pontine and mesencephalic tegmen- tum were known to comprise particularly important components of the 'Ascending Reticular Activating System.' Electrolytic lesions of this area resulted in severe deficits in behavioral arousal and cortical acti- vation indicative of wakefulness 41'42. Later, neurons within the oral and caudal pontine tegmentum were also shown to be critically involved in the generation of the state of paradoxical or rapid eye movement (PS or REM) sleep, by elimination of the state fol- lowing lesions within this area 8'35'52. With the advent of histochemical techniques, it was discovered that catecholamine-containing neu- rons were located within the pontomesencephalic tegmentum and gave rise to very widespread projec- tions, such as to suggest that they may represent an integral component of systems important in wakeful- Correspondence: B.E. Jones, Neuroanatomy Laboratory, Montreal Neurological Institute, 3801 University Street, Montreal, Qu6., Canada H3A 2B4. 0006-8993/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)