Voltage-Sensitive Dye Imaging Reveals Dynamic Spatiotemporal Properties of Cortical Activity after Spontaneous Muscle Twitches in the Newborn Rat

Abstract

Spontaneous activity in the developing brain contributes to its maturation, but how this activity is coordinated between distinct cortical regions and whether it might reflect developing sensory circuits is not well understood. Here, we address this question by imaging the spread and synchronization of cortical activity using voltage-sensitive dyes (VSDs) in the developing rat in vivo. In postnatal day 4 -6 rats (n ϭ 10), we collected spontaneous changes in VSD signal that reflect underlying membrane potential changes over a large craniotomy (50 mm 2 ) that encompassed both the sensory and motor cortices of both hemispheres. Bursts of depolarization that occurred approximately once every 12 s were preceded by spontaneous twitches of the hindlimbs and/or tail. The close association with peripheral movements suggests that these bursts may represent a slow component of spindle bursts, a prominent form of activity in the developing somatosensory cortex. Twitch-associated cortical activity was synchronized between subregions of somatosensory cortex, which reflected the synchronized twitching of the limbs and tail. This activity also spread asymmetrically, toward the midline of the brain. We found that the spatial and temporal structure of such spontaneous cortical bursts closely matched that of sensory-evoked activity elicited via direct stimulation of the periphery. These data suggest that spontaneous cortical activity provides a recurring template of functional cortical circuits within the developing cortex and could contribute to the maturation of integrative connections between sensory and motor cortices.

Self-Generated Movements with “Unexpected” Sensory Consequences

“…Twitch movements may be particularly well suited to this task because, unlike wake movements, they are produced discretely against a background of muscle atonia, both of which enhance signal-to-noise ratio [19]. Our results further suggest that the high fidelity of twitching depends upon the suspension of corollary discharge mechanisms, providing the infant with ideal conditions for activity-dependent development of the spinal cord [35], cerebellum [23], and forebrain [20–22, 36]. The information provided by twitching limbs may also enable the construction and calibration of internal models and predictive codes, which are thought to be essential for flexible and efficient sensorimotor control throughout the lifespan [37–39].…”

The Epigenetics of Stroke Recovery and Rehabilitation: From Polycomb to Histone Deacetylases

“…A map shift in the mediolateral axis is consistent with reorganization within contiguous areas of the motor cortex, while anteroposterior shifts indicate recruitment of neighboring nonprimary motor areas such as the premotor cortex or postcentral cortex [34,35]. Elegant imaging techniques by the laboratories of Dijkhuizen [36,37] and Murphy [38] have confirmed significant functional magnetic resonance imaging (fMRI) or voltage-sensitive dye responses in the infarct periphery ipsilesional to the stroke in animals. Equally elegant labeling of sprouting axons after stroke in the + ATPase.…”

Neurovascular coupling develops alongside neural circuits in the postnatal brain

“…In the adult brain, complex bilateral patterns of brain-wide spontaneous neural activity were observed, consistent with the results of previous studies using voltagesensitive dyes in the adult brain, and interpreted to represent brain-wide network activity. 15,34,37,39 In the same mice, hemodynamics across development mirrored those seen in rats: No localized increases in blood flow were observed at P7, despite the presence of strong, localized neural activity. By P10, only small correlated increases in blood flow were observed.…”