Developmental “awakening” of primary motor cortex to the sensory consequences of movement

Abstract

SUMMARYBefore primary motor cortex (M1) develops its motor functions, it behaves like a somatosensory area. Here, by recording from neurons in the forelimb representation of M1 in postnatal day (P) 8-12 rats, we demonstrate a rapid change in the types of movements that trigger sensory responses. At P8-10, M1 neurons respond overwhelmingly to sleep-related twitches of the forelimb, but the same neurons do not respond to forelimb movements when the animal is awake. Then, only two days later, M1 neurons suddenly respond to feedback from wake movements; this transition results from a change in sensory gating by the external cuneate nucleus. Also, at P12, the onset of local cortical inhibition leads to fewer M1 neurons responding to twitches; pharmacological disinhibition unmasks the more robust twitch responsiveness observed at P8. Thus, M1 initially establishes a somatosensory framework that lays a foundation for later-emerging motor control and plasticity.

Twitches emerge postnatally during quiet sleep in human infants and are synchronized with sleep spindles

“…23 In mammals, M1 develops much later than is commonly realized. 24,25 In humans, the late onset of M1 functionality dramatically reveals itself in infants who have experienced a perinatal stroke, which is the leading cause of hemiplegic cerebral palsy (CP). 26 Because of the protracted postnatal development of M1 and its descending connections, the disabling effects of CP are not evident until at least 4-8 months after birth.…”

Self-generated whisker movements drive state-dependent sensory input to developing barrel cortex

“…Previous studies have identified behavioral state as a factor that moderates the relationship between self-generated movements and neural activity. Specifically, in infant rats before postnatal day (P) 11, whereas sensory feedback from limb movements during wake only weakly activates sensorimotor cortex, sensory feedback from limb twitches during active sleep triggers strong cortical responses [5][6][7]. However, in many studies of activity in developing somatosensory cortex, either behavioral state was not measured [4,9,10] or the subjects were anesthetized [11][12][13].…”

“…As described previously [6,30], a pup with a visible milk band was removed from the litter and anesthetized with isoflurane gas (3-5%; Phoenix Pharmaceuticals, Burlingame, CA). All whiskers on the left side of the snout, except those in the C row, were trimmed ( Figure 1A).…”

“…As described previously [5,6], nuchal EMG and behavior were used to assess behavioral state (the experimenter was blind to the neurophysiological record when scoring behavior). The wake state was defined by the presence of high-amplitude movements of the limbs against a background of high nuchal muscle tone.…”

“…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][6][7]. Thus, perhaps inattention to behavioral state leads to failures to detect movement-driven activity [8].…”