Early motor activity drives spindle bursts in the developing somatosensory cortex

Abstract

Sensorimotor coordination emerges early in development. The maturation period is characterized by the establishment of somatotopic cortical maps, the emergence of long-range cortical connections, heightened experience-dependent plasticity and spontaneous uncoordinated skeletal movement. How these various processes cooperate to allow the somatosensory system to form a three-dimensional representation of the body is not known. In the visual system, interactions between spontaneous network patterns and afferent activity have been suggested to be vital for normal development. Although several intrinsic cortical patterns of correlated neuronal activity have been described in developing somatosensory cortex in vitro, the in vivo patterns in the critical developmental period and the influence of physiological sensory inputs on these patterns remain unknown. We report here that in the intact somatosensory cortex of the newborn rat in vivo, spatially confined spindle bursts represent the first and only organized network pattern. The localized spindles are selectively triggered in a somatotopic manner by spontaneous muscle twitches, motor patterns analogous to human fetal movements. We suggest that the interaction between movement-triggered sensory feedback signals and self-organized spindle oscillations shapes the formation of cortical connections required for sensorimotor coordination.

Early Development of the Thalamic Inhibitory Feedback Loop in the Primary Somatosensory System of the Newborn Mice

“…Interestingly spontaneous 10 Hz spindles were recorded in newborn rat S1 cortex (Khazipov et al, 2004). Their intrinsic frequency is unaffected by GABAergic antagonists applied in S1 cortex (Minlebaev et al, 2007(Minlebaev et al, , 2009, and they are correlated with nVPM neuronal activity (Khazipov et al, 2004), suggesting that they are generated in the thalamus and that they bear similarities with the adult cortical 7-15 Hz spindles. The adult spindles are generated during early stages of sleep by a thalamic inhibitory feedback loop between the GABAergic nucleus reticularis thalami (nRT) and the glutamatergic nVPM (Fuentealba and Steriade, 2005).…”

“…They are associated with a correlated activity in the nVPM, and their intrinsic frequency is unaffected by cortical applications of GABA A R antagonists, suggesting that the spindles are generated by subcortical circuits (Khazipov et al, 2004;Minlebaev et al, 2007). In the adult, the sleep spindles are generated by the nVPM-nRT loop (Steriade, 2005).…”

Development of human locomotion

“…In addition, spontaneous motor activity at an early developmental stage may facilitate the self-organization of neural circuits at both spinal and supra-spinal levels [21]. Thus, motor activity modulates the spinal circuits of central pattern generators (CPG) and those of nociceptive withdrawal reflexes [23], and it also modulates cortical somatosensory maps in a somatotopic manner [24]. Once established, spinal CPGs underlie fetal movements [22], but developing supra-spinal structures (such as the transient cortical subplate) presumably also play a role in more complex sequences of general movements, as demonstrated by the abnormality of general movements in human fetuses with brain disorders [10].…”

Interaction between neocortical and hippocampal networks via slow oscillations

“…The emerging thalamic spindles are transferred to the neocortex via topographic thalamo-cortical projections, and the spatially contiguous or distinct thalamic oscillations are synchronized by cortico-thalamic feedback (Kim et al, 1995;. Thalamo-cortical spindles represent the first organized pattern in the neocortex in newborn rats and pre-term human babies (Khazipov et al, 2004;Hanganu et al, 2006;Milh et al, 2006), although these early spindles are confined spatially. After the establishment of longrange cortico-cortical connections, spindles typically occur virtually synchronously across wide areas of the thalamus and cortex (Verzeano and Negishi, 1960;Bal et al, 2000).…”