Prenatal and Postnatal Development of GABAergic Neurons in the Spinal Cord Revealed by Green Fluorescence Protein Expression in the GAD67-GFP Knock-In Mouse

Abstract

To gain better insight into the ontogenic function of γ-aminobutyric acid (GABA) in the mouse spinal cord, it is necessary to know the developmental pattern of GABAergic neurons. In the present study, we examined the temporal and spatial developmental changes of GABAergic neurons at the cervical level of the spinal cord by using a glutamic acid decarboxylase 67 (GAD67)-green fluorescence protein (GFP) knock-in mouse. We found that GFP-positive GABAergic neurons appeared at embryonic day (E) 11.5 in the ventral region of the spinal cord and became abundant in the whole future gray matter at E12. Thereafter, GFP-positive neurons increased progressively in number and extended from ventral to dorsal regions. The intensity of GFP-positive neurons in the dorsal horn peaked at E17. After birth, GFP-positive neurons were mainly restricted to the dorsal gray matter and also decreased in the staining intensity. At postnatal day 14, the distribution pattern of GFP immunoreactivity was similar to that of GABAergic neurons in adult spinal cord. Taken together, the present results suggest that the GFP immunoreactivity, and thus the expression of GABA, undergoes a ventral-to-dorsal shift in the spinal cord during development. The functional significance of GFP-positive GABAergic neurons in the developing spinal cord is discussed.