Development of Twitching in Sleeping Infant Mice Depends on Sensory Experience

Abstract

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.

Sensory feedback synchronizes motor and sensory neuronal networks in the neonatal rat spinal cord

“…It should be noted that, both in the present and in previous studies7, spinal motor activity and associated spontaneous movements were assessed only during a relatively short period of time after deafferentation. However, changes in the normal expression and development of motor activity and behaviour are likely to occur at a longer time scale25, in line with the model of plasticity induced by sensory feedback in developing sensorimotor networks9.…”

Phantom Limbs, Neuroprosthetics, and the Developmental Origins of Embodiment

“…The latter view has more merit, but cannot easily explain the persistence of twitching into adulthood in various muscle groups across a diverse array of species. In contrast, when considered in its own right within the context of development, we find that twitching limbs exhibit complex spatiotemporal patterns across multiple joints, reflecting the emergence of motor synergies (Figure 1B) [16,17]. But for twitching to actually contribute to—rather than merely reflect—the development of the sensorimotor system, it is necessary that the twitch movements themselves trigger sensory feedback (i.e., reafference ) and that this feedback, in turn, activates sensorimotor structures.…”

Large Scale Cortical Functional Networks Associated with Slow-Wave and Spindle-Burst-Related Spontaneous Activity

“…Transecting the sensory regions of the spinal cord confirms that this effect reflects loss of ascending sensory, particularly proprioceptive, inputs (Jain et al, 2003). While it is hard to link this process to a particular pattern of brain activity, the altered development of the sensory cortex is only seen if the sensory feedback is disrupted during the first week of life, which overlaps with the peak period of expression of muscle twitches and spindle bursts (Blumberg et al, 2015). …”