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RESEARCH PROGRAM

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THE ROLE OF SLEEP IN LEARNING, MEMORY AND CEREBRAL PLASTICITY PROCESSES

Università degli Studi di Roma "La Sapienza"
Abstract
Since the first years of the past century it was shown that the strenghtening of memory traces could be facilitated by periods of sleep rather than equivalent periods of waking. The idea that sleep can play an important role in learning and memory processes has received empirical support by recent behavioral, neurophysiological and molecular genetic studies, both in humans and animals. Results not yet conclusive indicated a slow-wave sleep (SWS) involvement in the consolidation of verbal and non-verbal declarative memory. Similarly, it is not yet clear if the documented post-sleep improvements on procedural tasks are correlated to REM sleep, NREM sleep or to the sequence of both these stages. Based on this premises, our Research Program is aimed to investigate with an innovative approach, both in humans and in an animal model, the role of sleep in toto (as a whole) and of its specific stages in the memory processing of different tasks administered during wake. The Project is therefore integrated in one of the most important research areas in sleep psychophysiology at moment, characterized by an enormous heuristic value. The Research Program integrates a number of specific techniques and methodologies based on a consolidated experience of each Unit's participants, as showed by several international publications.
The first aim of the Research Program is to assess more directly the relationship between SWS and human memory consolidation, by means of a selective SWS >>>

Principal Investigator
Mario BERTINI Universita' degli Studi di ROMA
Research Objectives
In the light of several convergent results indicating a specific role for sleep stages on learning and memory processes, this Research Project will investigate in an innovative way, both in humans and in an animal model, the role of sleep as a whole and of its specific stages on memory processing of several tasks learned during waking.
The Program will use specific techniques and approaches based on the consolidated experience of each of the Units' participants, substantiated by a large number of international scientific publications. With respect to the current literature in this field, the Program will evaluate more directly the relationship between slow-wave sleep (SWS) and memory consolidation. In fact, the currently used design of early night/late night sleep (with a prevalence of, respectively, SWS and REM sleep) points out the involvement of SWS in the consolidation of verbal and non-verbal declarative memory. Such an evidence does not seem conclusive yet, since one cannot exclude that, as a consequence of the early night/late night design, the residual quantity of REM sleep or Stage 2 NREM slept during the first part of the night, can contribute to the observed effects. Moreover, it is not clear whether the observed improvements on visual discrimination tasks are correlated to REM sleep, to NREM sleep, or if the sequence of both NREM and REM is needed to obtain the maximum of effects. The aim of this part of the Research Program (Research Unit coordinated by >>>

First Results
RESEARCH UNIT: BERTINI
The data acquisition will be completed during the first phase. The main result expected in this phase is the complete suppression of SWS during the experimental nights (see Methods) without any other concomitant modification of the sleep structure and continuity.

RESEARCH UNIT: DE GENNARO
During the first phase, patient selection, electrode implantation and the complete data acquisition will be carried out.

RESEARCH UNIT: CICOGNA
The data acquisition will be completed during the first phase.

RESEARCH UNIT: MASCETTI
The refinement of the experimental procedure (to be used in the subsequent three experiments) will be completed during the first phase. The data acquisition of the first experiment, as well as a part of the second experiment (to be completed in the second Phase) will be also carried out during Phase one. As regards the first experiment, we expect that Mo-Un and binocular sleep amount will be different in the experimental and control groups, based on the differential importance of the two sleep phases for the recuperative process. As regards the second experiment, we expect to begin the data acquisition (see Phase 2).RESEARCH UNIT: BERTINI
With regard to the first study's aim (to assess, for the first time, the effects of different types of learning -declarative vs. procedural- on quantitative EEG parameters of sleep), we expect that the involvement of specific >>>

Timescale
24 months
National and international background
Although the function of sleep has generally been regarded to be restorative, it also plays an important role in learning and memory processes. Eighty years ago, Jenkins and Dallenbach (24) already provided evidence that strength of a memory trace may be enhanced by periods of sleep compared to equivalent periods of wakefulness. Sleep dependent benefits were intrepreted in terms of prevention of the acquisition of additional sensory inputs that would have impaired retention of previously acquired material. Such a "passive" hypothesis has been successively replaced by the idea that sleep is actively involved in memory consolidation. This concept was already clear in the Moruzzi's hypothesis (34) according to which sleep does not concern the fast recovery processes in routine synapses underlying stereotyped activities, but the slow recovery of "learned synapses" (i.e., new contacts between neurons). More recently, this idea received strong support by a large body of experimental evidence coming from studies in molecular genetics, neurophysiology and behavior in humans and other animals (31).
Studies on animal models can be divided in four broad categories: post-learning effects of sleep deprivation (mainly REM sleep deprivation); post-learning changes of sleep structure; relationships between sleep, brain development and brain plasticity; reactivation studies. Generally speaking, the studies referable to the first two categories have provided evidence for the role of >>>