title: Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms.
abstract: Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation.
authors.affiliation: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford Oxford, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Petzold
authors.affiliation: Neurosciences Area, CIMA, Universidad de Navarra Pamplona, Spain ; IdiSNA, Navarra Institute for Health Research Pamplona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Valencia
authors.affiliation: Department of Physiology, Faculty of Medicine University of Debrecen Debrecen, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Pál
authors.affiliation: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford Oxford, UK ; Center for Molecular and Behavioral Neuroscience, Rutgers University Newark, NJ, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Mena-Segovia
mesh_terms: D000818:Animals; D058256:Brain Waves / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D059329:Cholinergic Neurons / Q000502:physiology*; D055724:Electrophysiological Phenomena / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000502:physiology*; D045042:Pedunculopontine Tegmental Nucleus / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: arousal; brainstem; cholinergic neurons; network activity; oscillations; phasic