Date of Degree
PhD (Doctor of Philosophy)
Interdisciplinary Studies in Neural Systems and Development
The corpus callosum, the major interhemispheric fiber tract, mediates communication between homotopic regions within the primary somatosensory cortex (S1). Recently, in 1- to 6-day-old neonatal rats, brief bursts of high-frequency, oscillatory activity - called spindle-bursts (SBs) - were described in S1 following sensory feedback from endogenously generated sleep-related myoclonic twitch movements and exogenously generated peripheral stimulation. To determine whether interhemispheric communication via the corpus callosum modulates the expression of SBs during this early period of development and contributes to cortical organization and plasticity, we investigated the endogenous (spontaneous) expression and exogenous (evoked) activity of SBs in neonatal rats with intact or surgically severed callosal fibers (i.e., callosotomy; CCx). We used Ag/AgCl cortical surface electrodes in the S1-forelimb region of the cortex to measure neurophysiological and behavioral activity in both intact and CCx subjects across the sleep-wake cycle during the first two postnatal weeks of development.
Our results demonstrate, for the first time, that the corpus callosum modulates spontaneous and evoked activity between homotopic regions in S1 as early as 24-hours after birth. In addition, CCx disinhibits cortical activity, nearly doubling the rate of spontaneous SBs through, but not after, postnatal day 6 (P6). CCx also significantly and reliably disrupts the evoked response to peripheral stimulation of the forepaw. To examine the role of sleep-related twitches and their associated sensory feedback (SBs in S1) - modulated by the corpus callosum - in cortical development and plasticity, we performed CCx or sham surgeries at P1, P6, or P8, and tested subjects the day of surgery or over the ensuing week of recovery. Regardless of age, CCx immediately disrupted SBs evoked by forepaw stimulation. The P1 and P6 CCx groups exhibited full recovery after one week; in contrast, the P8 group did not exhibit recovery of function, thus indicating an abrupt decrease in cortical plasticity between P6 and P8. Together, these results provide the first evidence that sleep-related myoclonic twitches and the associated sensory feedback in S1 (SBs) contribute to cortical development, plasticity, and recovery of function after interhemispheric communication is disrupted by callosotomy. CCx-induced disinhibition of spontaneous SBs is a transient phenomenon whose disappearance coincides with the onset of increased intrinsic connectivity, establishment of excitatory-inhibitory balance, and diminished plasticity in S1. Our findings indicate that CCx-induced disinhibition of spontaneous twitch-related SBs and disruption of evoked response to peripheral stimulation serve as a bioassay of somatosensory cortical plasticity during the early postnatal period.
Callosotomy, Corpus callosum, GABA, Plasticity, Sleep, Somatosensory cortex
Copyright 2011 Amy Jo Marcano-Reik