Development of spontaneous mouth/tongue movement and related neural activity, and their repression in fetal mice lacking glutamate decarboxylase 67

Abstract

Spontaneous body movement starts at early fetal stage, at embryonic day (E) 12-15 in mice. In the present study, the movement of the head region was studied in E13-14 mice by in utero ultrasound imaging, together with the in vitro recording of underlying neural activities in the hypoglossal nerve and the ventral root of the upper cervical cord of an isolated brainstem-spinal cord preparation. The role of gamma-aminobutyric acid (GABA) in the generation of fetal movement was assessed using mice lacking GABA-synthesizing glutamate decarboxylase 67 (GAD67). At E14, mouth opening and tongue withdrawal were observed independently at frequency of 14/h each. This movement was rarely observed in the GAD67-deficient mouse. The intraventricular administration of picrotoxin or 3-mercaptopropionic acid abolished mouth opening in the wild-type mice. In a brainstem-spinal cord preparation, three types of neural discharge were recorded: mouth/tongue-moving burst, respiratory burst and irregular activity on the basis of their waveform, regularity in occurrence and concomitant muscle activity. In the GAD67-deficient mice, the occurrence of mouth/tongue-moving burst and irregular activity was inhibited to about 15 and 40% of those in the wild-type mice, respectively. Respiratory burst was slightly inhibited but the difference was not significant. Picrotoxin greatly reduced the frequency of mouth/tongue-moving burst. These results indicate that GABA is involved in rhythm generation in movement of the head region and support the hypothesis that cleft palate in the GAD67-deficient mouse is due to the impairment of mouth or tongue movement that assists palate formation.

Emergence of the Pre-Bötzinger Respiratory Rhythm Generator in the Mouse Embryo

“…Therefore, it likely represents a nonrespiratory activity. This is consistent with previous works obtained in rat ) and mice (Tsunekawa et al, 2005) combining recordings of C4 activity with either the diaphragm or the hypoglossal nerve activities and describing at early developmental stages generation of low-frequency discharges not related to respiratory activity.…”

Reduced Expression of GABA Transporter GAT3 in Helpless Rats, an Animal Model of Depression

“…It is not in line with the finding of reduced GAD67 expression in the cerebellum of patients with mood disorders [33]. GAD67 knockout animals do not show an affective phenotype [68]. In contrast, affective correlates have been described in GAD65-knockouts, for example altered conditioned fear behaviour [41], increased anxietylike behaviour in a light/dark avoidance test, reduced aggression between male animals, reduced forced-swimming-induced immobility [42], increased anxiety in the open field and the elevated zero maze [43].…”

Spontaneous depolarization waves of multiple origins in the embryonic rat CNS

“…Oscillations intermingled with nonoscillatory bursts also resemble the pattern of electrical discharges detected from the mouse spinal cord at E14.5 (Yvert et al, 2004). In experiments using rat and mouse embryos in vivo and in utero (Suzue & Shinoda, 1999;Tsunekawa et al, 2005) and in human fetuses (de Vries et al, 1982), spontaneous body movement has been observed and is considered to be related to the spontaneous electrical discharges recorded in vitro. To further exclude the possibility that the spontaneous activity simply appeared when the tissue was stained, we compared electrical discharges in unstained and stained preparations.…”