Abstract
Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine coreleasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play critical roles in regulating pain, locomotive movement, and respiratory rhythms. In this study, we first describe GABAergic and glycinergic transmission and inhibitory networks, consisting of three types of terminals in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with a specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated, and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many GABAergic neurons convert to a coreleasing state. The coreleasing neurons and terminals remain in the dorsal horn, whereas many ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.
Highlights
In the mature central nervous system (CNS), which includes the spinal cord, γaminobutyric acid (GABA), and glycine, are inhibitory neurotransmitters that negatively regulate neuronal activity [1,2,3,4]
The glycine transporter 2 (GlyT2) knockout mice die from lack of glycine during the second postnatal week [46,47], which suggests that de novo synthesis by serine hydroxymethyltransferase (SHMT) is not sufficient for glycinergic neurotransmission [4,12,48], and glycine in the neurons may be dominantly transported from extracellular space through blood–brain barrier
In the CNS, the change in membrane potential exerted by Gamma-aminobutyric acid (GABA) and glycine is determined by the intracellular chloride ion concentration ([Cl− ]i ), which is regulated by the balance of two different chloride cotransporters, Na+ -K+ -Cl− cotransporter 1 (NKCC1)
Summary
In the mature central nervous system (CNS), which includes the spinal cord, γaminobutyric acid (GABA), and glycine, are inhibitory neurotransmitters that negatively regulate neuronal activity [1,2,3,4]. (3) removal system, and (4) mechanisms underlying inhibitory transmission In the latter half of the review, we will focus on morphological development and demonstrate the processes of how mature networks are established through the following neuronal differentiation processes: GABAergic and glycinergic neurons are born in the ventricular zone, migrate in the gray matter, extend their dendrites and axons, and form synapses. During these processes, the neuronal types alter the composition of the receptor subunits changes, the removal system matures, and the action of both neurotransmitters shifts from excitatory to inhibitory
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