Distinct development of GABA system in the ventral and dorsal horns in the embryonic mouse spinal cord

• Published in: Brain research Vol. 1486; pp. 39 - 52
• Main Authors: Kosaka, Yoshinori, Kin, Hidemichi, Tatetsu, Masaharu, Uema, Itsuki, Takayama, Chitoshi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 27.11.2012; Elsevier
• Subjects: adults; Animals; Anterior Horn Cells - cytology; Anterior Horn Cells - embryology; Anterior Horn Cells - physiology; Axonogenesis; Axons; Biological and medical sciences; Brain; butyric acid; Cervical cord; Development. Senescence. Regeneration. Transplantation; Developmental stages; Dorsal horn; Embryogenesis; Embryonic Development - physiology; Embryos; Female; fetus; Fundamental and applied biological sciences. Psychology; GABAergic Neurons - cytology; GABAergic Neurons - physiology; GABAergic synapse; gamma -Aminobutyric acid; gamma -Aminobutyric acid transporter; gamma-Aminobutyric Acid - biosynthesis; gamma-Aminobutyric Acid - chemistry; gamma-Aminobutyric Acid - physiology; Glutamate decarboxylase; glutamic acid; Glutamic acid decarboxylase (GAD); immunohistochemistry; Mice; Mice, Inbred C57BL; Morphogenesis; Motor systems; Neurogenesis - physiology; Neurology; Neurons; Neurotransmitters; Posterior Horn Cells - cytology; Posterior Horn Cells - embryology; Posterior Horn Cells - physiology; potassium chloride; Potassium chloride co-transporter 2 (KCC2); Pregnancy; Spinal cord; Spinal Cord - cytology; Spinal Cord - embryology; Spinal Cord - physiology; synapse; Synapses; Synaptogenesis; Ventral horn; Vertebrates: nervous system and sense organs; Vesicular GABA transporter (VGAT); Marginal zone; de; Ventral horn; ABC; DH; KCC2; VZ; E; Central nervous system; CNS; Glycine; VGAT; GABAergic neuronal group 1–4; Mantle layer; GABAergic synapse; Gly; WM; γ-Amino butyric acid; Posterior funiculus; Glutamic acid decarboxylase (GAD); Embryonic day; Potassium chloride co-transporter 2; Ventricular zone; Dorsal horn; ML; CC; G1–G4; Cervical cord; Potassium chloride co-transporter 2 (KCC2); AF; Central canal; Lateral funiculus; Glutamic acid decarboxylase; GAD; MZ; Phosphate buffer; White matter; Avidin-biotin-peroxidase-complex; Dendrite; PB; VH; PF; Anterior funiculus; GABA; LF; Vesicular GABA transporter (VGAT); Vesicular GABA transporter; Embryo; Spinal cord; Lyases; Anterior spinal horn; Posterior spinal horn; Carboxy-lyases; Development; Carrier protein; Enzyme; Rodentia; KCC2 co-transporter; Glutamate decarboxylase; Potassium chloride; Carbon-carbon lyases; Vertebrata; Synapse; Mammalia; Mouse; Animal; Neurotransmitter
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2012.10.003

Abstract In the adult brain, γ -amino butyric acid (GABA) is an inhibitory neurotransmitter, whereas it acts as an excitatory transmitter in the immature brain, and may be involved in morphogenesis. In the present study, we immunohistochemically examined the developmental changes in GABA signaling in the embryonic mouse cervical spinal cord. Glutamic acid decarboxylase and GABA were markers for GABA neurons. Vesicular GABA transporter was a marker for GABAergic and glycinergic terminals. Potassium chloride cotransporter 2 was a marker for GABAergic inhibition. We found five points: (1) In the ventral part, GABA neurons were divided into three groups. The first differentiated group sent commissural axons after embryonic day 11 (E11), but disappeared or changed their transmitter by E15. The second and third differentiated groups were localized in the ventral horn after E12, and sent axons to the ipsilateral marginal zone. There was a distal-to-proximal gradient in varicosity formation in GABAergic axons and a superficial-to-deep gradient in GABAergic synapse formation in the ventral horn; (2) In the dorsal horn, GABA neurons were localized after E13, and synapses were diffusely formed after E15; (3) GABA may be excitatory for several days before synapses formation; (4) There was a ventral-to-dorsal gradient in the development of GABA signaling. The GABAergic inhibitory network may develop in the ventral horn between E15 and E17, and GABA may transiently play crucial roles in inhibitory regulation of the motor system in the mouse fetus; (5) GABA signaling continued to develop after birth, and GABAergic system diminished in the ventral horn.