Sleep is a poorly understood behavior that predominates during infancy but is studied almost exclusively in adults. One perceived impediment to investigations of sleep early in ontogeny is the absence of state-dependent neocortical activity. Nonetheless, in infant rats, sleep is reliably characterized by the presence of tonic (i.e., muscle atonia) and phasic (i.e., myoclonic twitching) components; the neural circuitry underlying these components, however, is unknown. Recently, we described a medullary inhibitory area (MIA) in week-old rats that is necessary but not sufficient for the normal expression of atonia. Here we report that the infant MIA receives projections from areas containing neurons that exhibit state-dependent activity. Specifically, neurons within these areas, including the subcoeruleus (SubLC), pontis oralis (PO), and dorsolateral pontine tegmentum (DLPT), exhibit discharge profiles that suggest causal roles in the modulation of muscle tone and the production of myoclonic twitches. Indeed, lesions in the SubLC and PO decreased the expression of muscle atonia without affecting twitching (resulting in “REM sleep without atonia”), whereas lesions of the DLPT increased the expression of atonia while decreasing the amount of twitching. Thus, the neural substrates of infant sleep are strikingly similar to those of adults, a surprising finding in light of theories that discount the contribution of supraspinal neural elements to sleep before the onset of state-dependent neocortical activity.

Rapid eye movements (REMs), traditionally measured using the electrooculogram (EOG), help to characterize active sleep in adults. In early infancy, however, they are not clearly expressed. Here we measure extraocular muscle activity in infant rats at 3 days of age (P3), P8, and P14-15 in order to assess the ontogeny of REMs and their relationship with other forms of sleep-related phasic activity. We find that the causal relationship between extraocular muscle twitches and REMs strengthens during the first two postnatal weeks, reflecting increased control of the extraocular muscles over eye movements. As early as P3, however, phasic bursts of extraocular muscle twitching occur in synchrony with twitching in other muscle groups, producing waves of phasic activity interspersed with brief periods of quiescence. Surprisingly, the tone of the extraocular muscles, invisible to standard EOG measures, fluctuates in synchrony with the tone of other muscle groups; focal electrical stimulation within the dorsolateral pontine tegmentum, an area that has been shown to contain wake-on neurons in P8 rats, results in the simultaneous activation of high tone in both nuchal and extraocular muscles. Finally, when state-dependent neocortical electroencephalographic activity was observed at P14, it had already integrated fully with sleep and wakefulness as defined using electromyographic criteria alone; this finding is not consistent with the notion that active sleep in infants at this age is "half-activated." All together, these results indicate exquisite temporal organization of sleep soon after birth and highlight the possible functional implications of homologous activational states in striated muscle and neocortex. KeywordsREM; atonia; myoclonic twitching; electroencephalogram; rat Sleep and wakefulness are discriminated in adult placental mammals using measures of eye movements, muscle tone, and neocortical activity. This trio of indicators is thought to provide necessary and sufficient information for categorizing sleep-wake states in adults, but its usefulness for categorizing these states in infants is limited (Rechtschaffen & Kales, 1968). Indeed, although sleep predominates during infancy (Roffwarg et al., 1966;Jouvet-Mounier et al., 1970), the idiosyncratic nature of infant sleep poses unique challenges . For example, before the end of the second postnatal week, infant rats do not exhibit state-dependent electroencephalographic (EEG) activity (Gramsbergen, 1976;Corner & Mirmiran, 1990;Frank & Heller, 1997), a feature of infant sleep that has contributed to its characterization as "disorganized," "diffuse," and produced by distinct neurophysiological mechanisms (Adrien & Lanfumey, 1984;Frank & Heller, 1997 Work from our laboratory has shown that nuchal electromyography (EMG) alone is sufficient for defining sleep-wake states during early infancy (Karlsson & Blumberg, 2002;Karlsson et al., 2004;. Most recently, it was shown in week-old rats that sleep and wake states identified in this way are governed by neural mec...

Light influences the daily patterning of behavior by entraining circadian rhythms and through its acute effects on activity levels (masking). Mechanisms of entrainment are quite similar across species, but masking can be very different. Specifically, in diurnal species, light generally increases locomotor activity (positive masking), and in nocturnal ones, it generally suppresses it (negative masking). The intergeniculate leaflet (IGL), a subdivision of the lateral geniculate complex, receives direct retinal input and is reciprocally connected with the primary circadian clock, the suprachiasmatic nucleus (SCN). Here, we evaluated the influence of the IGL on masking and the circadian system in a diurnal rodent, the Nile grass rat (Arvicanthis niloticus), by determining the effects of bilateral IGL lesions on general activity under different lighting conditions. To examine masking responses, light or dark pulses were delivered in the dark or light phase, respectively. Light pulses at Zeitgeber time (ZT) 14 increased activity in control animals but decreased it in animals with IGL lesions. Dark pulses had no effect on controls, but significantly increased activity in lesioned animals at ZT0. Lesions also significantly increased activity, primarily during the dark phase of a 12:12 light/dark cycle, and during the subjective night when animals were kept in constant conditions. Taken together, our results suggest that the IGL plays a vital role in the maintenance of both the species-typical masking responses to light, and the circadian contribution to diurnality in grass rats.

Despite the predominance of sleep in early infancy, developmental science has yet to play a major role in shaping concepts and theories about sleep and its associated ultradian and circadian rhythms. Here we argue that developmental analyses help us to elucidate the relative contributions of the brainstem and forebrain to sleep-wake control and to dissect the neural components of sleep-wake rhythms. Developmental analysis also makes it clear that sleep-wake processes in infants are the foundation for those of adults. For example, the infant brainstem alone contains a fundamental sleep-wake circuit that is sufficient to produce transitions among wakefulness, quiet sleep, and active sleep. Also, consistent with the requirements of a “flip-flop” model of sleep-wake processes, this brainstem circuit supports rapid transitions between states. Later in development, strengthening bidirectional interactions between the brainstem and forebrain contribute to the consolidation of sleep and wake bouts, the elaboration of sleep homeostatic processes, and the emergence of diurnal or nocturnal circadian rhythms. The developmental perspective promoted here critically constrains theories of sleep-wake control and provides a needed framework for the creation of fully realized computational models. Finally, with a better understanding of how this system is constructed developmentally, we will gain insight into the processes that govern its disintegration due to aging and disease.