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

Kosaka, Yoshinori; Kin, Hidemichi; Tatetsu, Masaharu; Uema, Itsuki; Takayama, Chitoshi

doi:10.1016/j.brainres.2012.10.003

Cited by 18 publications

(38 citation statements)

References 57 publications

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“…We also provide evidence that the earliest‐born C‐neurons that send axons toward the FP originate from the pd4‐p0 domains midway along the dorsoventral axis, suggesting that the axons originating from these C‐neuron subtypes pioneer the trajectory toward and across the midline. At least some of these pioneer neurons appear to be GABAergic, consistent with previous reports that describe expression of GABA biosynthetic enzymes in C‐neurons located in the early, intermediate mouse and rat spinal cord (Kosaka, Kin, Tatetsu, Uema, & Takayama, ; Phelps, Alijani, & Tran, ).…”

Section: Discussionsupporting

confidence: 89%

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse

Tulloch

Teo

Carvajal

et al. 2019

J of Comparative Neurology

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The two sides of the nervous system coordinate and integrate information via commissural neurons, which project axons across the midline. Commissural neurons in the spinal cord are a highly heterogeneous population of cells with respect to their birthplace, final cell body position, axonal trajectory, and neurotransmitter phenotype. Although commissural axon guidance during development has been studied in great detail, neither the developmental origins nor the mature phenotypes of commissural neurons have been characterized comprehensively, largely due to lack of selective genetic access to these neurons. Here, we generated mice expressing Cre recombinase from the Robo3 locus specifically in commissural neurons. We used Robo3 Cre mice to characterize the transcriptome and various origins of developing commissural neurons, revealing new details about their extensive heterogeneity in molecular makeup and developmental lineage. Further, we followed the fate of commissural neurons into adulthood, thereby elucidating their settling positions and molecular diversity and providing evidence for possible functions in various spinal cord circuits. Our studies establish an important genetic entry point for further analyses of commissural neuron development, connectivity, and function.

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Section: Discussionsupporting

confidence: 89%

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse

Tulloch

Teo

Carvajal

et al. 2019

J of Comparative Neurology

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“…51 In addition, the electrophysiological properties of GABAergic neurons in the spinal cord could be changed during development. 22,52–55 However, the primary inputs to GABAergic neurons in lamina II didn’t display significant changes between young (P21) mice and adult (P49) mice. 56…”

Section: Discussionmentioning

confidence: 98%

Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice

Liu

Zhang

et al. 2021

Mol Pain

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Background Spinal GABAergic neurons act as a critical modulator in sensory transmission like pain or itch. The monosynaptic or polysynaptic primary afferent inputs onto GABAergic neurons, along with other interneurons or projection neurons make up the direct and feed-forward inhibitory neural circuits. Previous research indicates that spinal GABAergic neurons mainly receive excitatory inputs from Aδ and C fibers. However, whether they are controlled by other inhibitory sending signals is not well understood. Methods We applied a transgenic mouse line in which neurons co-expressed the GABA-synthesizing enzyme Gad65 and the enhanced red fluorescence (td-Tomato) to characterize the features of morphology and electrophysiology of GABAergic neurons. Patch-clamp whole cell recordings were used to record the evoked postsynaptic potentials of fluorescent neurons in spinal slices in response to dorsal root stimulation. Results We demonstrated that GABAergic neurons not only received excitatory drive from peripheral Aβ, Aδ and C fibers, but also received inhibitory inputs driven by Aδ and C fibers. The evoked inhibitory postsynaptic potentials (eIPSPs) mediated by C fibers were mainly Glycinergic (66.7%) as well as GABAergic mixed with Glycinergic (33.3%), whereas the inhibition mediated by Aδ fibers was predominately both GABA and Glycine-dominant (57.1%), and the rest of which was purely Glycine-dominant (42.9%). Conclusion These results indicated that spinal GABAergic inhibitory neurons are under feedforward inhibitory control driven by primary C and Aδ fibers, suggesting that this feed-forward inhibitory pathway may play an important role in balancing the excitability of GABAergic neurons in spinal dorsal horn.

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“…GABA or GAD immunohistochemistry [55][56][57] and GAD-green fluorescent protein (GFP) labeling [58] demonstrated that the density of GABAergic neurons is high in the dorsal horn and moderate in the middle part of gray matter central part, whereas GA-BAergic neurons are scarce or in the ventral horn. The distribution of GABAergic terminals is almost the same as that of GABAergic neurons, with high density observed in the dorsal horn (Fig.…”

Section: Gabaergic and Glycinergic Transmission In The Mature Spinal Cordmentioning

confidence: 99%

“…1H) [9,53,[63][64][65]. Total inhibitory terminals, which are detected as VGAT (VIAAT)-positive dots, are homogeneously and ubiquitously distributed in the gray matter [55]. GABA and glycine play distinct roles in motor and sensory functions in the complex network in the dorsal [66,67] and ventral horns [68].…”

Section: Gabaergic and Glycinergic Transmission In The Mature Spinal Cordmentioning

confidence: 99%

“…In the mature CNS, which includes the spinal cord, KCC2 is highly expressed on the membranes of neuronal cell bodies and dendrites (Fig. 2C) [55], and its expression level is very high compared with that of NKCC1 [72][73][74]. Thus, in the mature spinal cord, the [Cl -]i is low enough for GABA and glycine to act as inhibitory neurotransmitters [55,75].…”

Section: Regulation Of Gabaergic and Glycinergic Action By Chloride Transportersmentioning

confidence: 99%

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Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord

Shimizu-Okabe¹,

Kobayashi²,

Kim³

et al. 2021

Preprint

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Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine co-releasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play key roles in the regulation of pain, locomotive movement, and respiratory rhythms. Herein, we first describe GABAergic and glycinergic transmission and inhibitory networks, which consist of three types of terminals, in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with 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 of GABAergic neurons convert to co-releasing state. The co-releasing neurons and terminals remain in the dorsal horn, whereas many of co-releasing ones 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.

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

Cited by 18 publications

References 57 publications

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse

Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice

Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord

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

Cited by 18 publications

References 57 publications

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3Cre mouse

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3Cre mouse

Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice

Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord

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Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse