Large-scale synchronized activity in the embryonic brainstem and spinal cord

Abstract

In the developing central nervous system, spontaneous activity appears well before the brain responds to external sensory inputs. One of the earliest activities is observed in the hindbrain and spinal cord, which is detected as rhythmic electrical discharges of cranial and spinal motoneurons or oscillations of Ca(2+)- and voltage-related optical signals. Shortly after the initial expression, the spontaneous activity appearing in the hindbrain and spinal cord exhibits a large-scale correlated wave that propagates over a wide region of the central nervous system, maximally extending to the lumbosacral cord and to the forebrain. In this review, we describe several aspects of this synchronized activity by focusing on the basic properties, development, origin, propagation pattern, pharmacological characteristics, and possible mechanisms underlying the generation of the activity. These profiles differ from those of the respiratory and locomotion pattern generators observed in the mature brainstem and spinal cord, suggesting that the wave is primordial activity that appears during a specific period of embryonic development and plays some important roles in the development of the central nervous system.

Keywords: brainstem; development; embryo; spinal cord; spontaneous activity; synchronization.

Figure 1

(A) Electrical recording of the spontaneous activity in the chick embryo. The signal was recorded from a brainstem-whole spinal cord preparation dissected from a stage 27 (E5.5) embryo with a glass micro-suction electrode applied to the root of the vagus nerve. (B) Optical imaging of the spontaneous activity in the rat embryo. The whole brain-spinal cord preparation dissected from an E16 embryo was stained with a voltage-sensitive dye NK2761, and optical recording was made by a 1020-element photodiode array system (Momose-Sato et al., 2001a). At the bottom, a color-coded representation of the maximum signal amplitudes (left) and waveforms (right) of the optical signals are shown. The vertical line in the signal waveforms indicates the onset of the spontaneous electrical discharge detected from the vagus nerve (N.X). Reproduced from Momose-Sato et al. (2007, 2009).

Figure 2

Pseudocolor images of the spontaneous activity in the mouse embryo. Spatiotemporal patterns of the spontaneous wave were examined in an E12 brainstem-spinal cord preparation. Images (A) and (B) were acquired during two independent episodes in the same preparation. The signals on the right were detected from five positions indicated in the lower right insets. In (A), the activity was initiated in the upper cervical cord [green circle in the inset of (A)], while in (B), the wave originated in the lumbosacral cord [red oval in the inset of (B)]. G.V, trigeminal ganglion; G.VIII, vestibulo-cochlear ganglion; N.X, vagus nerve. Reproduced from Momose-Sato et al. (2012a).

Figure 3

(A) Color-coded representation of maximum signal amplitudes of the spontaneous activity in an E13 mouse embryo. (B) Spatial distribution of the spontaneous activity in an E14 mouse embryo. The activity was localized to restricted regions of the medulla (left), caudal spinal cord (middle), and midline of the brainstem (right), which corresponds to the parafacial respiratory group, central pattern generator of locomotion, and midline raphe, respectively. The maximum amplitude of the optical signal is presented with color. (C) When bicuculline (10 μM) was applied to the E14 mouse preparation, spontaneous activity appeared in the rostral cord and spread over the brainstem and spinal cord, which was similar to the spatiotemporal pattern of the synchronized wave observed at the earlier stages. G.VIII, vestibulo-cochlear ganglion; N.X, vagus nerve. Reproduced from Momose-Sato et al. (2012a,b).