Pontine Waves Accompanied by Short Hippocampal Sharp Wave-Ripples During Non-rapid Eye Movement Sleep.

Ponto-geniculo-occipital or pontine (P) waves have long been recognized as an electrophysiological signature of rapid eye movement (REM) sleep. However, P-waves can be observed not just during REM sleep, but also during non-REM (NREM) sleep. Recent studies have uncovered that P-waves are functionally coupled with hippocampal sharp wave ripples (SWRs) during NREM sleep. However, it remains unclear to what extent P-waves during NREM sleep share their characteristics with P-waves during REM sleep and how the functional coupling to P-waves modulates SWRs. Here, we address these issues by performing multiple types of electrophysiological recordings and fiber photometry in both sexes of mice. P-waves during NREM sleep share their waveform shapes and local neural ensemble dynamics at a short (~100 milliseconds) timescale with their REM sleep counterparts. However, the dynamics of mesopontine cholinergic neurons are distinct at a longer (~10 seconds) timescale: although P-waves are accompanied by cholinergic transients, the cholinergic tone gradually reduces before P-wave genesis during NREM sleep. While P-waves are coupled to hippocampal theta rhythms during REM sleep, P-waves during NREM sleep are accompanied by a rapid reduction in hippocampal ripple power. SWRs coupled with P-waves are short-lived and hippocampal neural firing is also reduced after P-waves. These results demonstrate that P-waves are part of coordinated sleep-related activity by functionally coupling with hippocampal ensembles in a state-dependent manner.

Chronic postnatal monoamine oxidase inhibition affects affiliative behavior in rat pupso.

Monoamine neurotransmitters serotonin (5-HT), dopamine (DA), and noradrenaline (NA) act as important modulators of mammalian brain development and represent neurobiological substrates of affiliative behavior reflected in rat pups as a tendency to huddle or produce ultrasonic vocalizations (USV) when separated from the nest. Monoamines are metabolized through oxidative deamination catalyzed by the mitochondrial enzyme monoamine oxidase (MAO). In this study, we examined the consequences of postnatal MAO inhibition on affiliative behavior in rat pups. Pups received daily injections of either an irreversible non-selective MAO inhibitor tranylcypromine (TCP) or saline, from post-natal day (PND) 1 to PND 22. Quantitative and qualitative components of USV were analyzed on PNDs 10, 13 and 16 in order to determine the level of separation-induced anxiety and the modality of vocal communication. In comparison to control pups, TCP-treated pups displayed higher cortical 5-HT, DA and NA levels, higher peripheral 5-HT concentration, lower body mass throughout the pre-weaning period, higher isolation-induced drop in body temperature, and reduced total number of calls. Furthermore, they produced lower pitched calls of longer average duration without a preferable waveform. Our results demonstrate that chronic MAO inhibition by TCP primarily affects 5-HT concentrations, but also raises central catecholamine levels. They further indicate that disturbed monoaminergic homeostasis during early postnatal development leads to decreased weight-gain, compromised thermoregulation, and altered affiliative behavior in pre-weaning pups as reflected in reduced separation anxiety and inadequate vocal communication. Finally, they suggest a need for thorough examination of the potential effects of TCP and other monoamine inhibitors on the developing human brain.