Brain Research Bulletin 71 (2006) 4–9 The role of sleep in the consolidation of route learning in humans: A behavioural study Michele Ferrara a,∗ , Giuseppe Iaria b,c , Luigi De Gennaro c , Cecilia Guariglia c , Giuseppe Curcio c , Daniela Tempesta a , Mario Bertini c a Dipartimento di Medicina Interna e Sanit ` a Pubblica, Universit` a degli Studi dell’Aquila, Italy b Montreal Neurological Institute, McGill University, Montreal, Canada c Dipartimento di Psicologia, Universit` a di Roma “La Sapienza”, Italy Received 31 March 2006; received in revised form 25 May 2006; accepted 17 July 2006 Available online 15 August 2006 Abstract Considerable evidence support the role of sleep in learning and memory processes. In rodents, the relationships between sleep and memory consolidation have been extensively investigated by taking into account mainly spatial learning. On the contrary, in humans the relationship between sleep and spatial memory consolidation has so far been scarcely taken into account. Here, we investigated the importance of sleep in the consolidation of the spatial memory traces of a new route learned in a real-life unfamiliar environment. Fifty-one subjects followed a defined route in a neighbourhood they had never been to before. Then, they were tested in the laboratory in a sequence-recognition test requiring them to evaluate whether or not sequences of three views, taken along the route, represented a correct sequential order as seen while walking along the route. Participants were then assigned to one of three groups: the sleep group was retested after one night’s sleep, the sleep-deprived group was retested after a night of sleep deprivation, and the day-control group was retested the same day after 8 h of wakefulness. At retest, performance speed increased in all groups, whereas the accuracy in the sequence-recognition task was improved only in the sleep group: neither sleep deprivation nor the simple passage of time gave way to any performance improvement. These preliminary findings shed more light on the role of sleep in spatial memory consolidation by extending to humans the considerable evidence found in animals. © 2006 Elsevier Inc. All rights reserved. Keywords: Sleep; Spatial memory; Route learning; Navigation; Real environment 1. Introduction In 1966 Moruzzi suggested that sleep plays a critical role in memory consolidation by allowing the slow recovery of “learned synapses”, i.e. new contacts between neurons [11]. This early hypothesis received strong support by a large body of experi- mental evidence from molecular genetics, neurophysiological and behavioural studies in humans and animals [10]. Although the role of sleep in learning and memory pro- cesses has been strongly suggested [25], its specific contribution for memory remains hotly debated [21]: first, it is not clear ∗ Corresponding author at: Laboratorio di Psicofisiologia del Sonno, Dipar- timento di Psicologia, Universit` a degli Studi di Roma “La Sapienza”, Via dei Marsi 78, 00185 Roma, Italy. Tel.: +39 06 4991 7508; fax: +39 06 4451 667. E-mail address: michele.ferrara@cc.univaq.it (M. Ferrara). which aspects of memory function are affected by sleep and which processes underlie such a consolidation; second, it is not yet fully established how different types of memory are differentially influenced by the sleep stages and/or by their sequence. In rodents, the relations between sleep and memory consol- idation have been mostly studied by taking into account spatial memory, which is dependent on the hippocampus [12]. In par- ticular, post-training spontaneous reactivations of the so-called “place cells”, hippocampal neurons selectively firing when the animal occupies a specific spatial location within the environ- ment, have been extensively investigated. At the cellular level, it has been observed that neuronal ensembles activated during the waking behaviour are then re-activated during post-training sleep [13,16,20,22,30]. Consequently, it has been hypothesised that the offline replay of hippocampal activity during NREM sleep in rodents may be involved in the consolidation of newly 0361-9230/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2006.07.015