Embryonic development of GABAergic signaling in the mouse spinal trigeminal nucleus interpolaris

In the mature central nervous system, γ-amino butyric acid (GABA) is an inhibitory neurotransmitter, whereas during development, GABA induces depolarization. To examine the embryonic development of GABAergic transmission in the mouse spinal trigeminal nucleus interpolaris (SpVi), which receives sensory input from the face and is important in survival of rodents, we performed immunohistochemistry for three related molecules: glutamic acid decarboxylase (GAD), a marker of GABAergic neurons; vesicular GABA transporter (VGAT), a marker of GABAergic and glycinergic vesicles; and potassium chloride co-transporter 2 (KCC2), which shifts GABA action from excitatory to inhibitory. GAD-positive longitudinal projection fibers, where VGAT-positive dots were localized, were clearly discernible until embryonic day (E)17, and were markedly decreased in number on postnatal day 0. GAD-positive neurons were detected after E15, and GAD- and VGAT-positive axon varicosities were observed after E17. KCC2 immunolabeling was first localized in the dendrites and cell bodies of several neurons in the lateral part of the SpVi on E13 and throughout the nucleus on E17. These results suggest that the SpVi may first receive GABAergic projection fibers from extra-nuclear area before birth, and GABAergic interneurons may form synapses within the SpVi after E17. In addition, GABA action may gradually shift from excitatory to inhibitory between E13 and E17.