Pleasure: The missing link in the regulation of sleep.

Although largely unrecognized by sleep scholars, sleeping is a pleasure. This report aims first, to fill the gap: sleep, like food, water and sex, is a primary reinforcer. The levels of extracellular mesolimbic dopamine show circadian oscillations and mark the "wanting" for pro-homeostatic stimuli. Further, the dopamine levels decrease during waking and are replenished during sleep, in opposition to sleep propensity. The wanting of sleep, therefore, may explain the homeostatic and circadian regulation of sleep. Accordingly, sleep onset occurs when the displeasure of excessive waking is maximal, coinciding with the minimal levels of mesolimbic dopamine. Reciprocally, sleep ends after having replenished the limbic dopamine levels. Given the direct relation between waking and mesolimbic dopamine, sleep must serve primarily to gain an efficient waking. Pleasant sleep (i.e. emotional sleep), can only exist in animals capable of feeling emotions. Therefore, although sleep-like states have been described in invertebrates and primitive vertebrates, the association sleep-pleasure clearly marks a difference between the sleep of homeothermic vertebrates and cool blooded animals.

Effects of serotonergic drugs on locomotor activity and vigilance states in ring doves.

Serotonergic system is implicated on sleep-waking states in mammals. Since studies on serotonin regulation of sleep in birds are scarce, ring dove was chosen as experimental subject in the present work. The role of the neurotransmitter serotonin on vigilance states was studied in ring doves intraperitoneally treated with the 5-HT(1A) agonist 8-OH-DPAT, the 5-HT(1A) antagonist WAY100635 and the inhibitor of serotonin synthesis para-chlorophenylalanine (PCPA) by means of behavioural, electrophysiological and infrared actimetry criteria. 8-OH-DPAT (1 mg/kg) treatment increased locomotor activity, active waking and grooming states and reduced SWS and REM sleep. Pre-treatment with WAY100635 (0.5 mg/kg) prevented the effects induced by 8-OH-DPAT. Serotonin depletion induced by PCPA treatment (two consecutive injections of 300 mg/kg over two consecutive days) reduced locomotor activity, waking and grooming activity while increased both SWS and REM sleep. Moreover, 8-OH-DPAT (0.5 mg/kg) in PCPA treated ring doves produced a notable rise in the locomotor activity, active waking and grooming states, while it decreased sleep. Altogether, the results support the idea that serotonin plays an active role in wakefulness, probably through the activation of 5-HT(1A) receptors that increases wake activities and reduces sleep in ring doves.

Electroencephalogram functional connectivity between rat hippocampus and cortex after pilocarpine treatment.

The muscarinic agonist pilocarpine has been shown to increase the duration and total number of episodes presenting theta rhythm-simultaneously in hippocampus and cortex-in rats during the waking states. Theta waves are suggested to be involved in the flow of information between hippocampus and cortex during memory processes. This work investigates this functional interdependence using the spectral and phase synchronization analysis of the electroencephalogram (EEG) theta band recorded in these brain structures of rats after pilocarpine treatment. Pilocarpine was used at doses devoid of epilepticus-like seizures effects in conscious freely moving rats. The results showed that pilocarpine administration significantly increased the relative theta power during the waking states in the cortex, but not in the hippocampus of rats. Additionally, the EEG coherence between the hippocampal EEG theta band and that arising at the frontal cortex increased after pilocarpine treatment but only during the waking states. This result reveals an increase of the linear correlation between the theta waves of these two brain structures after pilocarpine treatment during the waking states. Moreover, phase synchronization results showed an effective phase locking with non-zero phase difference between hippocampus and frontal cortex theta waves that remained after pilocarpine treatment. Therefore, pilocarpine seems to reinforce the neural transmission waves from the hippocampus toward the cortex during waking. In conclusion, the present EEG study could suggest an effect of the muscarinic cholinergic agonist pilocarpine on the hippocampal-cortical functional connectivity.

Effects of pilocarpine on the cortical and hippocampal theta rhythm in different vigilance states in rats.

It has been suggested that theta rhythm gates the flow of information between the hippocampus and cortex during memory processes. The cholinergic system plays an important role in regulating vigilance states and in generating theta rhythm. This study aims to analyse the effects of the muscarinic agonist pilocarpine (120 and 360 microg, i.c.v.) on hippocampal and frontal cortical theta rhythm during several vigilance states in rats. Pilocarpine injection increased the duration and number of episodes with theta activity, particularly when theta rhythm appeared during waking states in the cortex and hippocampus simultaneously. It seems that the effects of pilocarpine are related to the appearance of cortical theta activity in waking states, and suggest that pilocarpine could modify the transference rate of information from the hippocampus to cortex in rats during wakefulness states, in relation to the postulated effect of cholinergic system modulating memory consolidation.

Comments on evolution of sleep and the palliopallial connectivity in mammals and birds.

This commentary is referred to the review signed by Rattemborg [N.C. Rattenborg, Evolution of slow wave sleep and palliopallial connectivity in mammals and birds. A hypothesis. Brain Res. Bull. 69 (2006) 20-29]. We propose that the review missed important aspects in relation to the characteristics of sleep in poikilotherm vertebrates and in the evolution of sleep. Poikilotherms continuously show an EEG dominated by slow waves, but its highest amplitude appears not during sleep, but during active waking. In addition, they show an arousal reaction which consists in an increase in EEG amplitude and synchrony, opposite to mammals and birds. As a consequence, most of the conclusions proposed in the review should be rejected.

Antioxidant response analysis in the brain after pilocarpine treatments.

Cholinergic and gabaergic systems play an important role generating electroencephalographic activity and regulating vigilance states. Pilocarpine is a cholinergic agonist commonly used to induce seizures and an epilepticus-like state in rodents. A relationship between status epilepticus and reactive oxygen species has been also suggested which could result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage as well as the antioxidant enzyme response in cortex and hippocampus after the administration of an intraperitoneal (350 mg/kg) and an intracerebroventricular (360 microg, 1 microl) pilocarpine injection in rats. The GABA agonist muscimol (1 mg/kg, i.p.), with described neuroprotective properties, was used as a negative control. Only systemic pilocarpine induced oxidative damage. Malondialdehyde levels, as a marker of lipid peroxidation (LP), increased in both regions (55-56%). Catalase (52-80%) and superoxide dismutase (53-60%) activities also rose in both regions but glutathione peroxidase activity only increased in cortex (45%). Glutathione reductase and caspase-3 activity did not change. In conclusion, systemic pilocarpine produced oxidative brain damage, whereas local pilocarpine brain injection had no effects. Moreover, the enzymatic determinations performed in this study are a good tool to study brain injury in pharmacological manipulations such as the ones used in short recording EEG studies.

[The work of Santiago Ramón y Cajal in the Revista Trimestral Micrográfica (Trabajos del Laboratorio de Investigaciones Biológicas)]. / La obra de Santiago Ramón y Cajal en Revista Trimestral Micrográfica (Trabajos del Laboratorio de Investigaciones Biológicas).

AIM: This paper is based on a study of Revista Trimestral Micrografica (Trabajos del Laboratorio de Investigaciones Biologicas) between its creation by Santiago Ramon y Cajal in 1896 and his death in 1934. DEVELOPMENT: The journal Revista Trimestral Micrografica was the main way in which Santiago Ramon y Cajal and his school published their work since its creation. Ramon y Cajal created the journal for two main reasons: first, he needed a rapid system to publish his own work; second, the journal could serve to encourage his pupils. The journal published many important reports defending the neuronal theory which expanded the cellular one to include the nervous system.

[Interrelations between sleep and the immune status]. / Interrelaciones entre el sueño y el estado inmune.

INTRODUCTION: The idea of the healing effects of the sleep over the disease is quite extended. Besides, the sleep and the circadian rhythms cause deep changes on the immune function. Reciprocally, the sleep also suffers deep changes when the immune system is challenged during an external aggression. DEVELOPMENT: This review shows some of the data supporting both observations. From the relationships between the sleep and the immune system, it has been proposed that one function of sleep is just to support the immune defense. However, an important fraction of the relationships between sleep and immune function might be a response to the stress produced both during the sleep disorders and when the organism activates the immune defense. Moreover, the epidemiological evidence only shows negligible results when contrasting the amount of sleep and the life expectancy. CONCLUSION: It seems thus probable that the relationships between sleep and immune function are only a reflect of additional factors, such as stress, which cause deep changes in sleep and immunity.

Interrelaciones entre el sueño y el estado inmune / Interrelations between sleep and the immune status

Introducción. Se cree que el sueño ejerce efectos beneficiosos sobre el sistema inmune. También hay evidencias firmes de que el sueño y los ritmos circadianos determinan cambios en el estado del sistema inmune. Recíprocamente, cuando el sistema inmune está afectado por una agresión externa, el sueño sufre importantes modificaciones. Desarrollo. Se presentan algunos de los datos que soportan las observaciones anteriores. De estas interrelaciones algunos autores consideran que una de las funciones del sueño es mantener las defensas inmunes. Sin embargo, una gran parte de las interacciones entre sueño y sistema inmune puede estar determinada por el estrés que se produce, tanto cuando el sueño está perturbado, como cuando el organismo sufre una agresión que determina una activación de las defensas inmunitarias. Además, la evidencia epidemiológica muestra que la esperanza de vida sufre muy pocos cambios en las personas que duermen más o menos que la mayoría de la población. Conclusión. Parece probable que las interacciones entre el sueño y el estado inmune no sean más que reflejos de otros factores que, como el estrés, ejercen profundos efectos sobre ambos

Introduction. The idea of the healing effects of the sleep over the disease is quite extended. Besides, the sleep and the circadian rhythms cause deep changes on the immune function. Reciprocally, the sleep also suffers deep changes when the immune system is challenged during an external aggression. Development. This review shows some of the data supporting both observations. From the relationships between the sleep and the immune system, it has been proposed that one function of sleep is just to support the immune defense. However, an important fraction of the relationships between sleep and immune function might be a response to the stress produced both during the sleep disorders and when the organism activates the immune defense. Moreover, the epidemiological evidence only shows negligible results when contrasting the amount of sleep and the life expectancy. Conclusion. It seems thus probable that the relationships between sleep and immune function are only a reflect of additional factors, such as stress, which cause deep changes in sleep and immunity

[The evolution of sleep: birds at the crossroads between mammals and reptiles]. / La evolución del sueño: las aves en la encrucijada entre mamíferos y reptiles.

INTRODUCTION: The evolution of sleep is one of the mysteries surrounding the sleep. Since the discovery of the two phases in the mammalian sleep, NREM and REM, the sleep researchers have unsuccessfully tried to understand their origin and the causes of the sleep duality. Looking for an answer to these questions, the sleep of reptiles (the parental group of mammals) and birds (also descending from reptiles) has been studied. As a result, NREM and REM were found in birds but not in reptiles, and the question remains thus unresolved. DEVELOPMENT AND CONCLUSIONS: This review presents a critical analysis of the published sleep studies developed in birds and points to a possible cause of the conflict: considerable doubts can be cast on the existence of the two sleep phases in birds. If birds turn to have only one sleep phase, they would have a very similar sleep to that of reptiles. As a consequence, the two phases, REM and NREM, would be exclusive of mammals, and both would have appeared as a consequence of the evolutionary changes in the development of the brain from reptiles to mammals.

La evolución del sueño: las aves en la encrucijada entre mamíferos y reptiles / The evolution of sleep: birds at the crossroads between mammals and reptiles

Introducción. La evolución del sueño es uno más de los misterios que envuelven el sueño. Desde el descubrimiento de las dos fases del sueño de mamíferos, REM y no REM, se intentó –con pocos resultados– comprender el origen de las dos fases y las razones por las cuales se mantiene la dualidad del sueño. Buscando la respuesta a estas preguntas se estudió el sueño de los reptiles, el grupo antecesor de los mamíferos, y de las aves, otro grupo que también desciende de los reptiles. El resultado es que las dos fases se han hallado en las aves, pero no han podido demostrarse en los reptiles, por lo que el misterio sigue sin resolverse. Desarrollo y conclusiones. En la presente revisión se analizan de forma crítica los resultados más conocidos del sueño de las aves y se apunta una solución para el conflicto: es posible que las dos fases de sueño tampoco existan en este grupo y, en consecuencia, su sueño sería similar al de los reptiles. Con esto, las dos fases, REM y no REM, serían exclusivas de los mamíferos y se habrían desarrollado como consecuencia de los cambios evolutivos en la estructura del cerebro

Introduction. The evolution of sleep is one of the mysteries surrounding the sleep. Since the discovery of the two phases in the mammalian sleep, NREM and REM, the sleep researchers have unsuccessfully tried to understand their origin and the causes of the sleep duality. Looking for an answer to these questions, the sleep of reptiles (the parental group of mammals) and birds (also descending from reptiles) has been studied. As a result, NREM and REM were found in birds but not in reptiles, and the question remains thus unresolved. Development and conclusions. This review presents a critical analysis of the published sleep studies developed in birds and points to a possible cause of the conflict: considerable doubts can be cast on the existence of the two sleep phases in birds. If birds turn to have only one sleep phase, they would have a very similar sleep to that of reptiles. As a consequence, the two phases, REM and NREM, would be exclusive of mammals, and both would have appeared as a consequence of the evolutionary changes in the development of the brain from reptiles to mammals

Why we sleep: the evolutionary pathway to the mammalian sleep.

The cause of sleep is a complex question, which needs first, a clear distinction amongst the different meanings of a causal relationship in the study of a given behavior, second, the requisites to be met by a suggested cause, and third, a precise definition of sleep to distinguish behavioral from polygraphic sleep. This review aims at clarifying the meaning of the question and at showing the phylogenetic origin of the mammalian and avian sleep. The phylogenetic appearance of sleep can be approached through a study of the evolution of the vertebrate brain. This began as an undifferentiated dorsal nerve, which was followed by the development of an anterior simplified brain and ended with the formation of the multilayered mammalian neocortex or the avian neostriate. The successive stages in the differentiation of the vertebrate brain produced, at least, two different waking types. The oldest one is the diurnal activity, bound to the light phase of the circadian cycle. Poikilotherms control the waking from the whole brainstem, where their main sensorymotor areas lie. Mammals developed the thalamocortical lines, which displaced the waking up to the cortex after acquiring homeothermy and nocturnal lifestyle. In order to avoid competence between duplicate systems, the early waking type, controlled from the brainstem, was suppressed, and by necessity was turned into inactivity, probably slow wave sleep. On the other hand, the nocturnal rest of poikilotherms most probably resulted in rapid eye movement sleep. The complex structure of the mammalian sleep should thus be considered an evolutionary remnant; the true acquisition of mammals is the cortical waking and not the sleep.

Main trends in rectal temperature during sleep. Hypnogram and thermogram.

Changes in sleep state and night-time body temperature were studied in 13 healthy young men. Temperature data showed serial dependence that was removed when considering three main segments of the thermogram: an initial rapid drop between 60 and 140 min after lights off, followed by a slower decrease to the thermal minimum and a final temperature increase until waking. The first segment was fitted by a two-term function, while the other two segments were fitted by linear regression. Temperature data obtained after fitting these models were stationary and used to calculate the fast Fourier transformation and the cross-correlation functions between the hypnogram and the thermogram of each subject. Attaining stationarity has unmasked short oscillations during sleep and some temperature series showed the presence of ultradian oscillations with a period of 90-100 min. Significant cross-correlations between sleep stages and body temperature were found, and the parameters of the two-term function fitted to the first temperature drop were related to the sign of the correlation and to that time series (sleep or temperature) which preceded the other during the night.

Reptilian waking EEG: slow waves, spindles and evoked potentials.

Signal spectral analysis procedures were used to compute the power spectrum of Gallotia galloti lizards EEG at different (5-35 degrees C) body temperatures. EEG power spectra were mainly characterized by a low frequency peak between 0.5 and 4 Hz which was present at the different body temperatures. A second spectral peak, corresponding to spindles of similar pattern to the sleep spindles of mammals, also appears in the spectra. The peak frequency of the spindles increased with the body temperature. Flash evoked potentials were characterized by a slow triphasic component upon which a spindle was superimposed, adopting a morphology similar to the K complexes of mammalian sleep. The characteristics of this EEG and evoked potentials support the hypothesis of homology between the waking state of the reptiles and the slow wave sleep of mammals.

Temperature drop and sleep: testing the contribution of SWS in keeping cool.

Sleep and body temperature characteristics were studied in man in baseline (B), 24 h-constant routine (CR) and recovery (R) after the CR. The sleep advanced and deepened the trough of the minimum temperature when compared with CR. No relevant difference in minimum body temperature, or in the slope of temperature decrease was found, however, between B and R sleeping nights. No correlation was found between the amount of slow wave sleep and body cooling. The results do not support a homeostatic role of slow wave sleep in brain and/or body cooling.

Developmental study of digestive motor response to dietary pattern in young broilers.

1. Gastrointestinal (GI) morphometry and motility were measured in young broilers (3, 8 and 15 days old) when they were submitted to three dietary patterns (ad libitum food, acute 48-hr fast and cumulative semi-starvation). 2. All GI regions were hypertrophied when acute or intermittent starvation were applied; lightly when acute starvation was applied and strongly with intermittent starvation. 3. All the 3-, 8- and 15-day-old acutely and intermittently starved chickens increased GI motility at the shortest times (0.5 and 1 hr) after the marker administration, but decreased GI motility at the longest times (2 and 4 hr). 4. The GI motor response of intermittently starved chicks was faster than the observed one in acutely starved chicks. The GI tract of intermittent starved chicks increased its motor response proportionally to the broilers age, while acutely starved chicks decreased their GI motility when the broilers age was increased. 5. A relationship between morphometrical and motor GI responses to dietary pattern has been inferred. From the gizzard and small bowel hypertrophy caused by intermittent starvation, an increased reflex GI motor response can be expected. Acute starvation only caused a light increase of GI motility, because it only increased the gizzard morphometry. 6. We concluded that young chicks respond to acute starvation by means of a short-term mechanism (an increase of GI motor reflexes) and responds to intermittent starvation by means of a medium- and long-term mechanism (a hypertrophy of GI tract and its subsequent increase of GI motor reflexes).

Effect of thyroidal state on the gastrointestinal transit and emptying of young broilers.

1. In newly hatched broilers, propylthiouracil and thyroid powder added to the diet produced hypothyroidism and hyperthyroidism, respectively. After 4-5 days of treatment body and thyroid weight changed, but no differences in body temperature were found. 2. The hyperthyroidal animals had high mortality rate and the hypothyroidal ones showed significantly lower glycemia values. 3. The gastrointestinal transit and emptying of 8 and 15 days old hypo-, hyper- and euthyroidal broiler chicks were measured using 14C-PEG-4000 as a marker. 4. Hypothyroidism prolonged GI transit and emptying, whereas hyperthyroidism modified these parameters in a way dependent of the elapsed time after the test meal: at 0.5 and 1 hr transit and emptying were quick, but at 2 and 4 hr the transit was slow. 5. Hyperthyroidism also delayed the transit of large bowel intraluminal contents in 15-day-old chickens. 6. These results are very similar to those of starvation, suggesting an important interaction between diencephalon, thyroid gland and GI motility in young chickens.