Sensorimotor Processing in the Newborn Rat Red Nucleus during Active Sleep

Abstract

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 GABA A , GABA B , 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.

Phantom Limbs, Neuroprosthetics, and the Developmental Origins of Embodiment

“…First, the motor cortex plays a negligible role in the production of movement—whether sleep or wake movement—at these early ages. This conclusion is wholly consistent with what is known about the brainstem generators of twitches [32] and the development of the cortical control of wake movements [34]. …”

“…(Activity in the basal ganglia is also likely to be influenced by twitch-related reafference, but this possibility has not yet been investigated.) Moreover, the red nucleus, which is part of a group of premotor structures in the mesodiencephalic junction [31], contributes to the production of twitches while also receiving reafference, suggesting that the integration of motor output and sensory feedback occurs even within this so-called motor nucleus [32]. It also notable that the nuclei within the mesodienchephalic junction are associated with the evolution of limbs and flapping fins, and appear to have been differentially recruited across species for the control of highly specialized structures such as the human hand and the elephant’s trunk [33].…”

“…It should be noted that a stimulation protocol that more closely mimics twitching would entail stimulation of the red nucleus and other brainstem premotor nuclei that are known to produce twitching [32]; however, these brainstem nuclei are much less accessible than motor cortex. But such details may not matter so long as the stimulation protocol results in the activation of sensorimotor circuits throughout the neuraxis in a discrete and somatotopically precise way.…”

A new view of “dream enactment” in REM sleep behavior disorder

“…RN recordings in week-old rats confirmed an important role for this nucleus in twitching [41]. In stark contrast with motor cortex at this age (see Figure 3), RN neurons fired bursts of action potentials just before wake-related limb movements and sleep-related limb twitches.…”

“…In week-old rats, unilateral pharmacological inactivation of the RN reduced twitching immediately but by only 50% [41]. And in adult cats, lesions of the red nucleus reduced twitching, but only transiently as twitching returned within several days [38,39].…”