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Animals must distinguish the sensory consequences of self-generated movements (reafference) from those of other-generated movements (exafference). Only self-generated movements entail the production of motor copies (i.e., corollary discharges), which are compared with reafference in the cerebellum to compute predictive or internal models of movement. Internal models emerge gradually over the first three postnatal weeks in rats through a process that is not yet fully understood. Previously, we demonstrated in postnatal day (P) 8 and P12 rats that precerebellar nuclei convey corollary discharge and reafference to the cerebellum during active (REM) sleep when pups produce limb twitches. Here, recording from a deep cerebellar nucleus (interpositus, IP) in P12 rats of both sexes, we compared reafferent and exafferent responses with twitches and limb stimulations, respectively. As expected, most IP units showed robust responses to twitches. However, in contrast with other sensory structures throughout the brain, relatively few IP units showed exafferent responses. Upon finding that exafferent responses occurred in pups under urethane anesthesia, we hypothesized that urethane inhibits cerebellar cortical cells, thereby disinhibiting exafferent responses in IP. In support of this hypothesis, ablating cortical tissue dorsal to IP mimicked the effects of urethane on exafference. Finally, the results suggest that twitch-related corollary discharge and reafference are conveyed simultaneously and in parallel to cerebellar cortex and IP. Based on these results, we propose that twitches provide opportunities for the nascent cerebellum to integrate somatotopically organized corollary discharge and reafference, thereby enabling the development of closed-loop circuits and, subsequently, internal models. [ABSTRACT FROM AUTHOR]

Primary motor cortex (M1) undergoes protracted development in mammals, functioning initially as a sensory structure. Throughout the first postnatal week in rats, M1 is strongly activated by self-generated forelimb movements--especially by the twitches that occur during active sleep. Here, we quantify the kinematic features of forelimb movements to reveal receptivefield properties of individual units within the forelimb region of M1. At postnatal day 8 (P8), nearly all units were strongly modulated by movement amplitude, especially during active sleep. By P12, only a minority of units continued to exhibit amplitude tuning, regardless of behavioral state. At both ages, movement direction also modulated M1 activity, though to a lesser extent. Finally, at P12, M1 population-level activity became more sparse and decorrelated, along with a substantial alteration in the statistical distribution of M1 responses to limb movements. These findings reveal a transition toward a more complex and informationally rich representation of movement long before M1 develops its motor functionality. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • In P8 rats, a linear decoder reliably predicts limb movements from M1 activity • At P12, M1 activity is continuous, and a nonlinear decoder is required • M1 activity is more sensitive to "lesions" and encoding scheme "transplants" at P12 • P12 marks the onset of more sparse and individualized M1 movement representations Cortical activity transitions from discontinuous to continuous around postnatal day 12 in rats. Glanz et al. use neural decoding to assess this transition's effect on sensory representations of limb kinematics in the primary motor cortex (M1). After the transition, M1 activity is more informationally dense, and its encoding scheme is more individualized. [ABSTRACT FROM AUTHOR]

Sensory feedback from sleep-related myoclonic twitches is thought to drive activity-dependent development in spinal cord and brain. However, little is known about the neural pathways involved in the generation of twitches early in development. The red nucleus (RN), source of the rubrospinal tract, has been implicated in the production of phasic motor activity during active sleep in adults. Here we hypothesized that the RN is also a major source of motor output for twitching in early infancy, a period when twitching is an especially abundant motor behavior. We recorded extracellular neural activity in the RN during sleep and wakefulness in 1-week-old unanesthetized rats. Neurons in the RN fired phasically before twitching and wake movements of the contralateral forelimb. A subpopulation of neurons in the RN exhibited a significant peak of activity after forelimb movement onset, suggesting reafferent sensory processing. Consistent with this observation, manual stimulation of the forelimb evoked RN responses. Unilateral inactivation of the RN using a mixture comprising GABAA, GABAB, and glycine receptor agonists caused an immediate and temporary increase in motor activity followed by a marked and prolonged decrease in twitching and wake movements. Altogether, these data support a causal role for the RN in infant motor behavior. Furthermore, they indicate that twitching, which is characterized by discrete motor output and reafferent input, provides an opportunity for sensorimotor integration and activity-dependent development of topography within the newborn RN. [ABSTRACT FROM AUTHOR]

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]

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]