Characteristic development of the GABA-removal system in the mouse spinal cord

Kim, J.; Kosaka, Yoshinori; Shimizu-Okabe, Chigusa; Niizaki, A.; Takayama, Chitoshi

doi:10.1016/j.neuroscience.2013.12.066

Cited by 10 publications

(24 citation statements)

References 58 publications

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“…Consistent with this notion, GAT-1 was found to be expressed in presynaptic terminals by us ( Fig. 3) and others (Kim et al 2014), and the global GABA uptake is increased in rats with the up-regulation of GAT-1 protein expression and downregulation of GAT-3 expression ( Fig. 5).…”

Section: Discussionsupporting

confidence: 84%

“…) and others (Kim et al . ), and the global GABA uptake is increased in rats with the up‐regulation of GAT‐1 protein expression and down‐regulation of GAT‐3 expression (Fig. ).…”

Section: Discussionmentioning

confidence: 89%

“…In one study on the rat spinal trigeminal nucleus, GAT-1 and GAT-3 are expressed in astrocytes (Ng and Ong 2001). Expressions of GAT-1 in presynaptic terminals and GAT-3 in astrocytes in the mouse spinal dorsal horn were recently reported (Kim et al 2014). Our current study on rats further confirmed that: (i) GAT-1 is positioned at the presynaptic terminals but not at the neuronal cell body, (ii) GAT-1 is also expressed in astrocytes, (iii) GAT-3 is only expressed in astrocytes, (iv) neither GAT-1 nor GAT-3 is expressed in microglia.…”

Section: Discussionmentioning

confidence: 99%

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Blocking the GABA transporter GAT‐1 ameliorates spinal GABAergic disinhibition and neuropathic pain induced by paclitaxel

Yadav

Yan

Maixner

et al. 2015

Journal of Neurochemistry

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Paclitaxel is a chemotherapeutic agent widely used for treating carcinomas. Patients receiving paclitaxel often develop neuropathic pain and have a reduced quality of life which hinders the use of this life-saving drug. In this study, we determined the role of GABA transporters in the genesis of paclitaxel-induced neuropathic pain using behavioral tests, electrophysiology, and biochemical techniques. We found that tonic GABA receptor activities in the spinal dorsal horn were reduced in rats with neuropathic pain induced by paclitaxel. In normal controls, tonic GABA receptor activities were mainly controlled by the GABA transporter GAT-1 but not GAT-3. In the spinal dorsal horn, GAT-1 was expressed at presynaptic terminals and astrocytes while GAT-3 was only expressed in astrocytes. In rats with paclitaxel-induced neuropathic pain, the protein expression of GAT-1 was increased while GAT-3 was decreased. This was concurrently associated with an increase of global GABA uptake. The paclitaxel-induced attenuation of GABAergic tonic inhibition was ameliorated by blocking GAT-1 but not GAT-3 transporters. Paclitaxel-induced neuropathic pain was significantly attenuated by the intrathecal injection of a GAT-1 inhibitor. These findings suggest that targeting GAT-1 transporters for reversing disinhibition in the spinal dorsal horn may be a useful approach for treating paclitaxel-induced neuropathic pain.

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Section: Discussionsupporting

confidence: 84%

“…) and others (Kim et al . ), and the global GABA uptake is increased in rats with the up‐regulation of GAT‐1 protein expression and down‐regulation of GAT‐3 expression (Fig. ).…”

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Blocking the GABA transporter GAT‐1 ameliorates spinal GABAergic disinhibition and neuropathic pain induced by paclitaxel

Yadav

Yan

Maixner

et al. 2015

Journal of Neurochemistry

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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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“…In contrast, uptake of released glycine into the astrocytic processes is mediated by GlyT1 and re-uptake of glycine into the presynaptic terminals is mediated by GlyT2. Because GAT-1 distribution is identical to that of the GA-BAergic terminals, GAT-1 is abundantly localized in the dorsal horn and sparsely localized in the ventral horn [70]. In contrast, GlyT2 is homogeneously distributed throughout the gray matter [53,71].…”

Section: Gabaergic and Glycinergic Transmission In The Mature Spinal Cordmentioning

confidence: 96%

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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Characteristic development of the GABA-removal system in the mouse spinal cord

Cited by 10 publications

References 58 publications

Blocking the GABA transporter GAT‐1 ameliorates spinal GABAergic disinhibition and neuropathic pain induced by paclitaxel

Blocking the GABA transporter GAT‐1 ameliorates spinal GABAergic disinhibition and neuropathic pain induced by paclitaxel

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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