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Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.

During sleep, humans experience the offline images and sensations that we call dreams, which are typically emotional and lacking in rational judgment of their bizarreness. However, during lucid dreaming (LD), subjects know that they are dreaming, and may control oneiric content. Dreaming and LD features have been studied in North Americans, Europeans and Asians, but not among Brazilians, the largest population in Latin America. Here we investigated dreams and LD characteristics in a Brazilian sample (n = 3,427; median age = 25 years) through an online survey. The subjects reported recalling dreams at least once a week (76%), and that dreams typically depicted actions (93%), known people (92%), sounds/voices (78%), and colored images (76%). The oneiric content was associated with plans for the upcoming days (37%), memories of the previous day (13%), or unrelated to the dreamer (30%). Nightmares usually depicted anxiety/fear (65%), being stalked (48%), or other unpleasant sensations (47%). These data corroborate Freudian notion of day residue in dreams, and suggest that dreams and nightmares are simulations of life situations that are related to our psychobiological integrity. Regarding LD, we observed that 77% of the subjects experienced LD at least once in life (44% up to 10 episodes ever), and for 48% LD subjectively lasted less than 1 min. LD frequency correlated weakly with dream recall frequency (r = 0.20, p < 0.01), and LD control was rare (29%). LD occurrence was facilitated when subjects did not need to wake up early (38%), a situation that increases rapid eye movement sleep (REMS) duration, or when subjects were under stress (30%), which increases REMS transitions into waking. These results indicate that LD is relatively ubiquitous but rare, unstable, difficult to control, and facilitated by increases in REMS duration and transitions to wake state. Together with LD incidence in USA, Europe and Asia, our data from Latin America strengthen the notion that LD is a general phenomenon of the human species.

. Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin. Am J Physiol Endocrinol Metab 290: E566 -E572, 2006; doi:10.1152/ajpendo.00427.2005.-Mating or vaginocervical stimulation [copulatory stimulus (CS)] induces two daily surges of the hormone prolactin (PRL) in rats. This unique secretory pattern of PRL surges is characteristic for the first half of pregnancy and is also present in ovariectomized (OVX) rats. Studies have shown that CS additionally provokes an acute release of the hormone oxytocin (OT).In this study, we tested whether a single injection of OT (iv) is sufficient to initiate the PRL secretion pattern of OVX/CS rats. Furthermore, we measured the 24-h profile of dopamine (DA) content in the anterior lobe of the pituitary gland, because DA is the major inhibitory factor of PRL secretion. The results indicated that a single injection of OT induces a PRL secretory rhythm and a DA release pattern similar to that initiated by CS. Immunocytochemical investigation showed that particular OTergic neurons in the hypothalamus express receptors for PRL, as well as for vasoactive intestinal polypeptide, which indicates an involvement in generating the PRL rhythm and entraining it to the ambient photoperiod. On the basis of this study, we suggest that the PRL-DA inhibitory feedback loop between lactotrophs and DAergic neurons plays a crucial role in generating the oscillatory PRL secretion pattern in CS rats. A timing signal, likely provided by the hypothalamic suprachiasmatic nucleus, entrains the autonomous PRL oscillation to a particular time of day. Mathematical modeling was used to illustrate the proposed network function. The experimental results further suggest an additional feedback mechanism in which certain hypothalamic OTergic neurons are influenced by PRL. dopamine; suprachiasmatic nucleus; mathematical modeling; lactotrophs THE EARLY PHASE OF PREGNANCY and pseudopregnancy in rats is characterized by two daily peaks of prolactin (PRL) secretion, referred to as nocturnal (at ϳ0300) and diurnal (at ϳ1700) surges (13,15,21). This unique secretory pattern is induced by the mating stimulus or vaginocervical stimulation [copulatory stimulus (CS)] and persists for ϳ10 days in pregnant (45) animals and 12 days in pseudopregnant animals (44). The increased PRL output is important in maintaining the structural and functional integrity of the corpus luteum, which, in turn, is responsible for progesterone synthesis (44). The PRL secretory pattern in CS rats entrains to photoperiod and can be shifted within limits under various lighting conditions (53). Furthermore, this pattern becomes free running in constant darkness, which demonstrates that the PRL rhythm is a true circadian rhythm (6).PRL secretion from lactotrophs, located in the anterior lobe of the pituitary gland, is controlled by a balance of PRLreleasing and -inhibiting hormones supplied to the pituitary gland from neurosecretory cells in the hypothalamus through the portal vasculature (1,15,28). Several in vivo and in vi...

Previous observations suggest the existence of 'Active sleep' in cephalopods. To investigate in detail the behavioral structure of cephalopod sleep, we video-recorded four adult specimens of Octopus insularis and quantified their distinct states and transitions. Changes in skin color and texture and movements of eyes and mantle were assessed using automated image processing tools, and arousal threshold was measured using sensory stimulation. Two distinct states unresponsive to stimulation occurred in tandem. The first was a 'Quiet sleep' state with uniformly pale skin, closed pupils, and long episode durations (median 415.2 s). The second was an 'Active sleep' state with dynamic skin patterns of color and texture, rapid eye movements, and short episode durations (median 40.8 s). 'Active sleep' was periodic (60% of recurrences between 26 and 39 min) and occurred mostly after 'Quiet sleep' (82% of transitions). These results suggest that cephalopods have an ultradian sleep cycle analogous to that of amniotes.

The brain stores memories by persistently changing the connectivity between neurons. Sleep is known to be critical for these changes to endure. Research on the neurobiology of sleep and the mechanisms of long-term synaptic plasticity has provided data in support of various theories of how brain activity during sleep affects long-term synaptic plasticity. The experimental findingsand therefore the theoriesare apparently quite contradictory, with some evidence pointing to a role of sleep in the forgetting of irrelevant memories, whereas other results indicate that sleep supports the reinforcement of the most valuable recollections. A unified theoretical framework is in need. Computational modeling and simulation provide grounds for the quantitative testing and comparison of theoretical predictions and observed data, and might serve as a strategy to organize the rather complicated and diverse pool of data and methodologies used in sleep research. This review article outlines the emerging progress in the computational modeling and simulation of the main theories on the role of sleep in memory consolidation.

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