Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline

Cholinergic basal forebrain structures are implicated in cortical arousal and regulation of the sleep–wake cycle. Cholinergic neurones are innervated by noradrenergic terminals, noradrenaline excites them via alpha‐1 receptors and microinjection of noradrenaline into the basal forebrain enhances wakefulness. However, it is not known to what extent the cholinergic versus non‐cholinergic basal forebrain projection neurones contribute to the arousing effects of noradrenaline. To elucidate the roles of cholinergic basal forebrain structures we administered methoxamine, an alpha‐1‐adrenergic agonist into the basal forebrain, in intact animals and again after selective destruction of the basal forebrain cholinergic cells by 192 IgG‐saporin. In eight male Han–Wistar rats implanted with electroencephalogram/electromyogram electrodes, a microdialysis probe targeted into the basal forebrain was perfused with artificial cerebrospinal fluid for 6 h on a baseline day, and with cerebrospinal fluid in the first and with methoxamine in the second 3‐h period of the subsequent day. The sleep–wake activity was recorded for 24 h on both days. Saporin was then injected into the basal forebrain and 2 weeks later the same experimental schedule (with cerebrospinal fluid and methoxamine) was repeated. In the intact animals, methoxamine exhibited a robust arousing effect and non‐rapid eye movement (NREM) and REM sleep was suppressed. Lesioning of the basal forebrain cholinergic neurones abolished almost completely the NREM sleep‐suppressing effect of methoxamine, whereas the REM sleep‐suppressing effect remained intact. Thus, the basal forebrain cholinergic neurones mediate, at least in part, cortical arousal and non‐REM sleep‐suppression, but they are not involved in the REM sleep‐suppressing effects of noradrenaline.     

Periodic properties of the histaminergic system of the mouse brain

Brain histamine is involved in the regulation of the sleep–wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1‐methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine‐N‐methyltransferase in C57BL/6J mice. In the C57BL/6J strain, histamine release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24‐h periodicity was observed. Brain tissue 1‐methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine‐N‐methyltransferase in the striatum and cortex did not show a 24‐h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12‐h periodicity. These results show that the activities of histamine‐metabolizing enzymes are not under simple direct circadian regulation. The complex and non‐uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness.     

The effects of maternal risk factors during pregnancy on the onset of sleep difficulties in infants at 3 months old

Sleep problems in young children are among the most common concerns reported to paediatricians. Sleep is thought to have important regulatory functions, and sleep difficulties in early childhood are linked to several psychosocial and physiological problems. Moreover, several prenatal factors have been found to influence infants’ sleep. Among them, most of the studies have been focused on maternal prenatal depression and/or anxiety as potential risk factors for sleep problems in childhood, whereas other relevant psychological factors during pregnancy have not received as much attention. Therefore, we aimed to examine the effect of several psychiatric maternal risk factors during pregnancy (i.e. symptoms of anxiety, depression, insomnia, alcohol use, seasonality, attention deficit and hyperactivity disorder and/or stressful life events) on the onset of some sleep problems related to sleep quality and sleep practices in 3‐month‐old infants. We examined 1,221 cases from a population‐based birth cohort, with subjective measures during pregnancy in mothers, and at 3 months after birth in the infants. The findings showed that all the maternal risk factors during pregnancy, except for symptoms of alcoholism and sleepiness, were related to sleep difficulties in infants. Interestingly, attention deficit and hyperactivity disorder symptomatology in mothers during pregnancy was the only variable that predicted more than two sleeping difficulties (i.e. long sleep‐onset latency, co‐sleeping with parents and irregular sleeping routines) at 3 months old. Our results highlight the relevance of maternal risk factors during pregnancy, and not only prenatal depression and/or anxiety, as variables to be considered when examining sleep difficulties in infants.