The Neural Substrates of Infant Sleep in Rats

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

Extraocular Muscle Activity, Rapid Eye Movements and the Development of Active and Quiet Sleep

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 measured 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 found that the causal relationship between extraocular muscle twitches and REMs strengthened 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 occurred 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, fluctuated 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, resulted 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 \u27half-activated.\u27 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

The Emergence of Somatotopic Maps of the Body in S1 in Rats: The Correspondence Between Functional and Anatomical Organization

Most of what we know about cortical map development and plasticity comes from studies in mice and rats, and for the somatosensory cortex, almost exclusively from the whisker-dominated posteromedial barrel fields. Whiskers are the main effector organs of mice and rats, and their representation in cortex and subcortical pathways is a highly derived feature of murine rodents. This specialized anatomical organization may therefore not be representative of somatosensory cortex in general, especially for species that utilize other body parts as their main effector organs, like the hands of primates. For these reasons, we examined the emergence of whole body maps in developing rats using electrophysiological recording techniques. In P5, P10, P15, P20 and adult rats, multiple recordings were made in the medial portion of S1 in each animal. Subsequently, these functional maps were related to anatomical parcellations of S1 based on a variety of histological stains. We found that at early postnatal ages (P5) medial S1 was composed almost exclusively of the representation of the vibrissae. At P10, other body part representations including the hindlimb and forelimb were present, although these were not topographically organized. By P15, a clear topographic organization began to emerge coincident with a reduction in receptive field size. By P20, body maps were adult-like. This study is the first to describe how topography of the body develops in S1 in any mammal. It indicates that anatomical parcellations and functional maps are initially incongruent but become tightly coupled by P15. Finally, because anatomical and functional specificity of developing barrel cortex appear

Evolution of mammalian sensorimotor cortex: Thalamic projections to parietal cortical areas in Monodelphis domestica

The current experiments build upon previous studies designed to reveal the network of parietal cortical areas present in the common mammalian ancestor. Understanding this ancestral network is essential for highlighting the basic somatosensory circuitry present in all mammals, and how this basic plan was modified to generate species specific behaviors. Our animal model, the short-tailed opossum (Monodelphis domestica), is a South American marsupial that has been proposed to have a similar ecological niche and morphology to the earliest common mammalian ancestor. In this investigation, we injected retrograde neuroanatomical tracers into the face and body representations of primary somatosensory cortex (S1), the rostral and caudal somatosensory fields (SR and SC), as well as a multimodal region (MM). Projections from different architectonically defined thalamic nuclei were then quantified. Our results provide further evidence to support the hypothesized basic mammalian plan of thalamic projections to S1, with the lateral and medial ventral posterior thalamic nuclei (VPl and VPm) projecting to S1 body and S1 face, respectively. Additional strong projections are from the medial division of posterior nucleus (Pom). SR receives projections from several midline nuclei, including the medial dorsal, ventral medial nucleus, and Pom. SC and MM show similar patterns of connectivity, with projections from the ventral anterior and ventral lateral nuclei, VPm and VPl, and the entire posterior nucleus (medial and lateral). Notably, MM is distinguished from SC by relatively dense projections from the dorsal division of the lateral geniculate nucleus and pulvinar. We discuss the finding that S1 of the short-tailed opossum has a similar pattern of projections as other marsupials and mammals, but also some distinct projections not present in other mammals. Further we provide additional support for a primitive posterior parietal cortex which receives input from multiple modalities

Representative traces of multi-unit activity in a P5 (A) and P15 (B) rat.

<p>A) Multi-unit activity in response to stimulation of both ipsilateral (left) and contralateral (right) vibrissae. Tic marks indicate the temporal pattern of stimulation. The inset box includes a depiction of S1 with the recording site indicated by an open circle (scale = 1 mm). B) Multi-unit activity in response to stimulation of toe 4 (left) and toe 5 (right) of the contralateral hindpaw. The receptive field for the neurons is indicated in gray on the schematic of the contralateral hindpaw. The inset box includes an illustration of S1 with the recording site marked by an open circle (scale = 1 mm).</p

List of Abbreviations.

<p>List of Abbreviations.</p

Receptive field progressions in P10 and P5 rats.

<p>A) Progressions of recording sites in S1 in a P10 rat (left) and corresponding receptive fields for neurons at those sites (right). In P10 rats, the topographic organization is imprecise. The receptive fields are very large and many receptive fields cover multiple body parts (i.e., sites 7–9). Vibrissae representations are found throughout S1 in inappropriate locations (i.e., sites 1, 2, 4 and 5). As recording sites progress from medial to lateral in the caudal portion of S1 (1–3) corresponding receptive fields were all on the ipsilateral vibrissae. Recording sites in the far medial location (4, 5), in what would be the hindpaw representation in the adult, had receptive fields on the ipsilateral or vibrissae. Recording sites in medial portions of S1 in what would normally be the forepaw representation (6–9) had receptive fields on the forepaw, split receptive fields on the upper body and vibrissae, bilateral vibrissae and face and vibrissae. B) Progressions of recording sites in S1 in a P5 rat (left) and corresponding receptive fields for neurons at those sites (right). In P5 rats there is no apparent topography. Receptive fields are large, and, when present on the limbs, encompass both hairy and glabrous portions of the paws. Receptive fields are also observed on both the contralateral and ipsilateral body parts. Vibrissae representations are prevalent and found throughout S1. As recording sites progress from medial to lateral in the caudal portion of S1 (1–3) corresponding receptive fields move from the contralateral vibrissae to the lateral trunk. Far medial recording sites (4–5) in what would normally be the hindpaw representation had receptive field on the vibrissae, and in one instance the dorsal and ventral hindpaw. More medial recording sites (6–8), in what would normally be the forepaw representation had receptive fields on the contralateral or bilateral vibrissae, and wrist and vibrissae. Compare this figure with the full map of the body illustrated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032322#pone-0032322-g001" target="_blank">Figure 1</a>. Conventions as in previous figures.</p

The topographic organization of the primary somatosensory area in adult rats.

<p>As in all other mammals examined, the contralateral body is represented from hindlimb to forelimb to face in a mediolateral progression. The individual toes of the hindpaw and digits of the forepaw are represented rostrally, the proximal limbs caudal to this and the trunk most caudally. In rats, there is a large magnification of the vibrissae of the face. In this and following figures, the head representation is shaded red, the forelimb representation is yellow, the hindlimb representation is green, and the trunk representation is blue. In this figure, unresponsive zones (UZ) are represented in black. Modified from Chapin and Lin, 1984.</p