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With our eyes closed, we can track a limb's moment-to-moment location in space. If this capacity relied solely on sensory feedback from the limb, we would always be a step behind because sensory feedback takes time: for the execution of rapid and precise movements, such lags are not tolerable. Nervous systems solve this problem by computing representations — or internal models — that mimic movements as they are happening, with the associated neural activity occurring after the motor command but before sensory feedback. Research in adults indicates that the cerebellum is necessary to compute internal models. What is not known, however, is when—and under what conditions—this computational capacity develops. Here, taking advantage of the unique kinematic features of the discrete, spontaneous limb twitches that characterize active sleep, we captured the developmental emergence of a cerebellar-dependent internal model. Using rats at postnatal days (P) 12, P16, and P20, we compared neural activity in the ventral posterior (VP) and ventral lateral (VL) thalamic nuclei, both of which receive somatosensory input but only the latter of which receives cerebellar input. At all ages, twitch-related activity in VP lagged behind the movement, consistent with sensory processing; similar activity was observed in VL through P16. At P20, however, VL activity no longer lagged behind movement but instead precisely mimicked the movement itself; this activity depended on cerebellar input. In addition to demonstrating the emergence of internal models of movement, these findings implicate twitches in their development and calibration through, at least, the preweanling period. [Display omitted] • Twitches trigger activity in thalamus and cortex beyond the early postnatal period • Twitch-related activity is spatiotemporally refined by the 3rd postnatal week • Motor thalamus activity reflects an internal model of a twitch • This internal model of movement depends on cerebellar output Internal models of movement enable the production of coordinated behavior; however, we do not know when internal models first develop. Using myoclonic twitches, movements that are produced exclusively during sleep, Dooley et al. establish the emergence of a cerebellar-dependent internal model of movement in motor thalamus of rats at 20 days of age. [ABSTRACT FROM AUTHOR]

In humans and other mammals, the stillness of sleep is punctuated by bursts of rapid eye movements (REMs) and myoclonic twitches of the limbs. 1 Like the spontaneous activity that arises from the sensory periphery in other modalities (e.g., retinal waves), 2 sensory feedback arising from twitches is well suited to drive activity-dependent development of the sensorimotor system. 3 It is partly because of the behavioral activation of REM sleep that this state is also called active sleep (AS), in contrast with the behavioral quiescence that gives quiet sleep (QS)—the second major stage of sleep—its name. In human infants, for which AS occupies 8 h of each day, 4 twitching helps to identify the state; 5–8 nonetheless, we know little about the structure and functions of twitching across development. Recently, in sleeping infants, 9 we documented a shift in the temporal expression of twitching beginning around 3 months of age that suggested a qualitative change in how twitches are produced. Here, we combine behavioral analysis with high-density electroencephalography (EEG) to demonstrate that this shift reflects the emergence of limb twitches during QS. Twitches during QS are not only unaccompanied by REMs, but they also occur synchronously with sleep spindles, a hallmark of QS. As QS-related twitching increases with age, sleep spindle rate also increases along the sensorimotor strip. The emerging synchrony between subcortically generated twitches and cortical oscillations suggests the development of functional connectivity among distant sensorimotor structures, with potential implications for detecting and explaining atypical developmental trajectories. [Display omitted] • In human infants, myoclonic twitches are a key component of active sleep • By 3 months of age, sleep spindles occur reliably during quiet sleep • Also around 3 months of age, twitches unexpectedly emerge during quiet sleep • When twitches occur during quiet sleep, they are synchronized with sleep spindles Myoclonic twitching is a characteristic component of active sleep, especially in early development. Sokoloff et al. discover that, beginning around 3 months of age in human infants, twitches emerge unexpectedly during quiet sleep. These twitches are synchronized with sleep spindles, thus implicating them in sensorimotor plasticity. [ABSTRACT FROM AUTHOR]

Summary Myoclonic twitches are jerky movements that occur exclusively and abundantly during active (or REM) sleep in mammals, especially in early development [ 1–4 ]. In rat pups, limb twitches exhibit a complex spatiotemporal structure that changes across early development [ 5 ]. However, it is not known whether this developmental change is influenced by sensory experience, which is a prerequisite to the notion that sensory feedback from twitches not only activates sensorimotor circuits but modifies them [ 4 ]. Here, we investigated the contributions of proprioception to twitching in newborn ErbB2 conditional knockout mice that lack muscle spindles and grow up to exhibit dysfunctional proprioception [ 6–8 ]. High-speed videography of forelimb twitches unexpectedly revealed a category of reflex-like twitching—comprising an agonist twitch followed immediately by an antagonist twitch—that developed postnatally in wild-types/heterozygotes, but not in knockouts. Contrary to evidence from adults that spinal reflexes are inhibited during twitching [ 9–11 ], this finding suggests that twitches trigger the monosynaptic stretch reflex and, by doing so, contribute to its activity-dependent development [ 12–14 ]. Next, we assessed developmental changes in the frequency and organization (i.e., entropy) of more-complex, multi-joint patterns of twitching; again, wild-types/heterozygotes exhibited developmental changes in twitch patterning that were not seen in knockouts. Thus, targeted deletion of a peripheral sensor alters the normal development of local and global features of twitching, demonstrating that twitching is shaped by sensory experience. These results also highlight the potential use of twitching as a uniquely informative diagnostic tool for assessing the functional status of spinal and supraspinal circuits. [ABSTRACT FROM AUTHOR]

In early development, active sleep is the predominant sleep state before it is supplanted by quiet sleep. In rats, the developmental increase in quiet sleep is accompanied by the sudden emergence of the cortical delta rhythm (0.5–4 Hz) around postnatal day 12 (P12). We sought to explain the emergence of the cortical delta by assessing developmental changes in the activity of the parafacial zone (PZ), a medullary structure thought to regulate quiet sleep in adults. We recorded from the PZ in P10 and P12 rats and predicted an age-related increase in neural activity during increasing periods of delta-rich cortical activity. Instead, during quiet sleep, we discovered sleep-dependent rhythmic spiking activity—with intervening periods of total silence—phase locked to a local delta rhythm. Moreover, PZ and cortical delta were coherent at P12 but not at P10. PZ delta was also phase locked to respiration, suggesting sleep-dependent modulation of PZ activity by respiratory pacemakers in the ventral medulla. Disconnecting the main olfactory bulbs from the cortex did not diminish cortical delta, indicating that the influence of respiration on delta at this age is not mediated indirectly through nasal breathing. Finally, we observed an increase in parvalbumin-expressing terminals in the PZ across these ages, supporting a role for local GABAergic inhibition in the PZ's rhythmicity. The unexpected discovery of delta-rhythmic neural activity in the medulla—when cortical delta is also emerging—provides a new perspective on the brainstem's role in regulating sleep and promoting long-range functional connectivity in early development. [Display omitted] • Neurons in the medullary parafacial zone (PZ) fire rhythmically during quiet sleep • Rhythmic PZ spiking activity is phase locked with a local delta rhythm (0.5–4 Hz) • PZ delta develops alongside cortical delta, and the two rhythms are coherent • Rhythmic spiking in the PZ is also phase locked with respiration Researchers have long sought evidence that the brainstem helps synchronize cortical rhythms. Ahmad et al. use infant rats spanning various ages to study the initial emergence of cortical delta during quiet sleep. Their findings demonstrate the expression of delta-rhythmic and breathing-related neural activity in the medulla that is coherent with cortical delta. [ABSTRACT FROM AUTHOR]

Cortical development is an activity-dependent process 1–3. Regarding the role of activity in the developing somatosensory cortex, one persistent debate concerns the importance of sensory feedback from self-generated movements. Specifically, recent studies claim that cortical activity is generated intrinsically, independent of movement 3 , 4. However, other studies claim that behavioral state moderates the relationship between movement and cortical activity 5–7. Thus, perhaps inattention to behavioral state leads to failures to detect movement-driven activity 8. Here, we resolve this issue by associating local field activity (i.e., spindle bursts) and unit activity in the barrel cortex of 5-day-old rats with whisker movements during wake and myoclonic twitches of the whiskers during active (REM) sleep. Barrel activity increased significantly within 500 ms of whisker movements, especially after twitches. Also, higher-amplitude movements were more likely to trigger barrel activity; when we controlled for movement amplitude, barrel activity was again greater after a twitch than a wake movement. We then inverted the analysis to assess the likelihood that increases in barrel activity were preceded within 500 ms by whisker movements: at least 55% of barrel activity was attributable to sensory feedback from whisker movements. Finally, when periods with and without movement were compared, 70%–75% of barrel activity was movement related. These results confirm the importance of sensory feedback from movements in driving activity in sensorimotor cortex and underscore the necessity of monitoring sleep-wake states to ensure accurate assessments of the contributions of the sensory periphery to activity in developing somatosensory cortex. • In newborn rats, self-generated whisker movements trigger barrel cortex activity • Larger whisker movements are more likely to trigger responses in barrel cortex • Movement-related cortical activity occurs more often during active sleep than wake • When pups don't move at all, there is a 3-fold reduction in cortical activity Some researchers have questioned whether sensory feedback from movements drives activity in developing somatosensory cortex. On the contrary, using infant rats, Dooley et al. establish that activity in barrel cortex depends critically on sensory feedback from whisker movements, particularly during active sleep. [ABSTRACT FROM AUTHOR]

Summary Neuronal oscillations comprise a fundamental mechanism by which distant neural structures establish and express functional connectivity. Long-range functional connectivity between the hippocampus and other forebrain structures is enabled by theta oscillations. Here, we show for the first time that the infant rat red nucleus (RN)—a brainstem sensorimotor structure—exhibits theta (4–7 Hz) oscillations restricted primarily to periods of active (REM) sleep. At postnatal day 8 (P8), theta is expressed as brief bursts immediately following myoclonic twitches; by P12, theta oscillations are expressed continuously across bouts of active sleep. Simultaneous recordings from the hippocampus and RN at P12 show that theta oscillations in both structures are coherent, co-modulated, and mutually interactive during active sleep. Critically, at P12, inactivation of the medial septum eliminates theta in both structures. The developmental emergence of theta-dependent functional coupling between the hippocampus and RN parallels that between the hippocampus and prefrontal cortex. Accordingly, disruptions in the early expression of theta could underlie the cognitive and sensorimotor deficits associated with neurodevelopmental disorders such as autism and schizophrenia. [ABSTRACT FROM AUTHOR]

Summary: Spontaneous activity in the sensory periphery drives infant brain activity and is thought to contribute to the formation of retinotopic and somatotopic maps [1–3]. In infant rats during active (or REM) sleep, brainstem-generated spontaneous activity triggers hundreds of thousands of skeletal muscle twitches each day [4]; sensory feedback from the resulting limb movements is a primary activator of forebrain activity [1]. The rodent whisker system, with its precise isomorphic mapping of individual whiskers to discrete brain areas, has been a key contributor to our understanding of somatotopic maps and developmental plasticity [5–7]. But although whisker movements are controlled by dedicated skeletal muscles [8, 9], spontaneous whisker activity has not been entertained as a contributing factor to the development of this system [10]. Here we report in 3- to 6-day-old rats that whiskers twitch rapidly and asynchronously during active sleep; furthermore, neurons in whisker thalamus exhibit bursts of activity that are tightly associated with twitches but occur infrequently during waking. Finally, we observed barrel-specific cortical activity during periods of twitching. This is the first report of self-generated, sleep-related twitches in the developing whisker system, a sensorimotor system that is unique for the precision with which it can be experimentally manipulated. The discovery of whisker twitching will allow us to attain a better understanding of the contributions of peripheral sensory activity to somatosensory integration and plasticity in the developing nervous system [11–13]. [Copyright &y& Elsevier]

The primary motor cortex (M1) exhibits a protracted period of development, including the development of a sensory representation long before motor outflow emerges. In rats, this representation is present by postnatal day (P) 8, when M1 activity is "discontinuous." Here, we ask how the representation changes upon the transition to "continuous" activity at P12. We use neural decoding to predict forelimb movements from M1 activity and show that a linear decoder effectively predicts limb movements at P8 but not at P12; instead, a nonlinear decoder better predicts limb movements at P12. The altered decoder performance reflects increased complexity and uniqueness of kinematic information in M1. We next show that M1's representation at P12 is more susceptible to "lesioning" of inputs and "transplanting" of M1's encoding scheme from one pup to another. Thus, the emergence of continuous M1 activity signals the developmental onset of more complex, informationally sparse, and individualized sensory representations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)