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

2022 ◽  
Vol 23 (2) ◽  
pp. 834
Author(s):  
Chigusa Shimizu-Okabe ◽  
Shiori Kobayashi ◽  
Jeongtae Kim ◽  
Yoshinori Kosaka ◽  
Masanobu Sunagawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Radial Glia ◽  
Ventricular Zone ◽  
Glycine Receptor ◽  
Ventral Horn ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Mouse Spinal Cord ◽  
Mature Mouse

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.

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

2021 ◽  
Author(s):  
Chigusa Shimizu-Okabe ◽  
Shiori Kobayashi ◽  
Jeongtae Kim ◽  
Yoshinori Kosaka ◽  
Masanobu Sunagawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Radial Glia ◽  
Ventricular Zone ◽  
Glycine Receptor ◽  
Ventral Horn ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Mouse Spinal Cord ◽  
Mature Mouse

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.

GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

2003 ◽  
Vol 98 (5) ◽  
pp. 1223-1230 ◽  
Author(s):  
Ryo Orii ◽  
Yoko Ohashi ◽  
Sunil Halder ◽  
Mariangela Giombini ◽  
Mervyn Maze ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Antinociceptive Effect ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Fischer Rats ◽  
The Brain ◽  
Gas Exposure

Background The study hypothesizes that nitrous oxide (N(2)O) releases opioid peptide in the brain stem, which results in inhibition of gamma-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of alpha2 adrenoceptor and indirect activation of GABAergic neurons through alpha1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N(2)O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N(2)O-induced antinociceptive effect. Methods Adult male Fischer rats were administered muscimol (GABA(A) receptor agonist) intracerebroventricularly (icv), gabazine (GABA(A) receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N(2)O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically. Results The N(2)O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N(2)O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord. Conclusions The GABAergic neurons modulate the antinociceptive effect of N(2)O in opposite directions at supraspinal and spinal levels. The pronociceptive effects of enhancement at the supraspinal GABAergic site predominate in response to systemically administered midazolam.

scholarly journals Glutamate Transporter GLAST Is Expressed in the Radial Glia–Astrocyte Lineage of Developing Mouse Spinal Cord

1997 ◽  
Vol 17 (23) ◽  
pp. 9212-9219 ◽  
Author(s):  
Takashi Shibata ◽  
Keiko Yamada ◽  
Masahiko Watanabe ◽  
Kazuhiro Ikenaka ◽  
Keiji Wada ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Radial Glia ◽  
Glutamate Transporter ◽  
Mouse Spinal Cord

Changes in serotonin-induced potentials during spinal cord development

1993 ◽  
Vol 69 (4) ◽  
pp. 1338-1349 ◽  
Author(s):  
L. Ziskind-Conhaim ◽  
B. S. Seebach ◽  
B. X. Gao
Keyword(s):  
Spinal Cord ◽  
Direct Action ◽  
Membrane Resistance ◽  
Ventral Horn ◽  
Repetitive Firing ◽  
Lumbar Spinal Cord ◽  
Receptor Subtypes ◽  
Gamma Aminobutyric Acid ◽  
Spinal Neurons ◽  
Lumbar Spinal

1. Motoneuron responses to serotonin (5-hydroxytryptamine, 5-HT), and the growth pattern of 5-HT projections into the ventral horn were studied in the isolated spinal cord of embryonic and neonatal rats. 2. 5-HT projections first appeared in lumbar spinal cord at days 16-17 of gestation (E16-E17) and were localized in the lateral and ventral funiculi. By E18, the projections had grown into the ventral horn, and at 1-2 days after birth they were in close apposition to motoneuron somata. 3. At E16-E17, slow-rising depolarizing potentials of 1-4 mV were recorded intracellularly in lumbar motoneurons in response to bath application of 5-HT. These potentials were not apparent after E18; at that time 5-HT generated long-lasting depolarizations with an average amplitude of 6 mV, and an increase of 11% in membrane resistance. Starting at E18, 5-HT also induced high-frequency fast-rising potentials that were blocked by antagonists of glutamate, gamma-aminobutyric acid, and glycine. 4. Motoneuron responses to 5-HT increased significantly after birth, when 5-HT produced an average depolarization of 19 mV and repetitive firing of action potentials. 5. Tetrodotoxin and high Mg2+ did not reduce the amplitude of the long-lasting depolarizations, which suggested that they were produced by direct action of 5-HT on motoneuron membrane. 6. At all developmental ages, 5-HT reduced the amplitude of dorsal root-evoked potentials. The suppressed responses were neither due to 5-HT-induced depolarization nor the result of a decrease in motoneuron excitability. 7. The pharmacological profile of 5-HT-induced potentials was studied with the use of various agonists and antagonists of 5-HT. The findings indicated that the actions of 5-HT on spinal neurons were mediated via multiple 5-HT receptor subtypes. 8. Our results suggested that 5-HT excited spinal neurons before 5-HT projections grew into the ventral horn. The characteristics of 5-HT-induced potentials changed, however, at the time when the density of 5-HT projections increased in the motor nuclei.

Antagonism of the Antinocifensive Action of Halothane by Intrathecal Administration of GABA-A Receptor Antagonists

1996 ◽  
Vol 84 (5) ◽  
pp. 1205-1214 ◽  
Author(s):  
Peggy Mason ◽  
Casey A. Owens ◽  
Donna L. Hammond
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Glycine Receptor ◽  
Intrathecal Administration ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Receptor Antagonists ◽  
Response Latencies ◽  
Halothane Concentration

Background The hind brain and the spinal cord, regions that contain high concentrations of gamma-aminobutyric acid (GABA) and GABA receptors, have been implicated as sites of action of inhalational anesthetics. Previous studies have established that general anesthetics potentiate the effects of gamma-aminobutyric acid at the GABAA receptor. It was therefore hypothesized that the suppression of nocifensive movements during anesthesia is due to an enhancement of GABAA receptor-mediated transmission within the spinal cord. Methods Rats in which an intrathecal catheter had been implanted 1 week earlier were anesthetized with halothane. Core temperature was maintained at a steady level. After MAC determination, the concentration of halothane was adjusted to that at which the rats last moved in response to tail clamping. Saline, a GABAA, a GABAB, or glycine receptor antagonist was then injected intrathecally. The latency to move in response to application of the tail clamp was redetermined 5 min later, after which the halothane concentration was increased by 0.2%. Response latencies to application of the noxious stimulus were measured at 7-min intervals during the subsequent 35 min. To determine whether these antagonists altered baseline response latencies by themselves, another experiment was conducted in which the concentration of halothane was not increased after intrathecal administration of GABAA receptor antagonists. Results Intrathecal administration of the GABAA receptor antagonists bicuculline (0.3 micrograms) or picrotoxin (0.3, 1.0 micrograms) antagonized the suppression of nocifensive movement produced by the small increase in halothane concentration. In contrast, the antinocifensive effect of the increase in halothane concentration was not attenuated by the GABAB receptor antagonist CGP 35348 or the glycine receptor antagonist strychnine. By themselves, the GABAA receptor antagonists did not alter response latency in rats anesthetized with sub-MAC concentrations of halothane. Conclusions Intrathecal administration of bicuculline or picrotoxin, at doses that do not change the latency to pinch-evoked movement when administered alone, antagonized the suppression of noxious-evoked movement produced by halothane concentrations equal to or greater than MAC. These results suggest that enhancement of GABAA receptor-mediated transmission within the spinal cord contributes to halothane's ability to suppress nocifensive movements.

scholarly journals Glycinergic Miniature Synaptic Currents and Receptor Cluster Sizes Differ Between Spinal Cord Interneurons

1999 ◽  
Vol 82 (1) ◽  
pp. 312-319 ◽  
Author(s):  
Sharon Oleskevich ◽  
Francisco J. Alvarez ◽  
Bruce Walmsley
Keyword(s):  
Spinal Cord ◽  
Glycine Receptor ◽  
Structural Features ◽  
Ventral Horn ◽  
Electrophysiological Recording ◽  
Rat Spinal Cord ◽  
Whole Cell Patch Clamp ◽  
Structural And Functional Properties ◽  
Receptor Clusters

The structural features of a synaptic connection between central neurons play an important role in determining the strength of the connection. In the present study, we have examined the relationship between the structural and functional properties of glycinergic synapses in the rat spinal cord. We have analyzed the structure of glycinergic receptor clusters on rat ventral horn interneurons using antibodies against the glycine receptor clustering protein, gephyrin. We have examined the properties of quantal glycinergic currents generated at these synapses using whole cell patch-clamp recordings of miniature postsynaptic inhibitory currents (mIPSCs) in rat spinal cord slices in vitro. Our immunolabeling results demonstrate that there is a considerable variability in the size of glycine receptor clusters within individual neurons. Furthermore there are large differences in the mean cluster size between neurons. These observations are paralleled closely by recordings of glycinergic mIPSCs. The mIPSC amplitude varies significantly within and between neurons. Results obtained using combined immunolabeling and electrophysiological recording on the same neurons show that cells with small glycine receptor clusters concurrently exhibit small mIPSCs. Our results suggest that the differences in the size of glycinergic receptor clusters may constitute an important factor contributing to the observed differences in mIPSC amplitude among spinal cord interneurons.

scholarly journals An in vitro functionally mature mouse spinal cord preparation for the study of spinal motor networks

1999 ◽  
Vol 816 (2) ◽  
pp. 493-499 ◽  
Author(s):  
Zhiyu Jiang ◽  
Kevin P Carlin ◽  
Robert M Brownstone
Keyword(s):  
Spinal Cord ◽  
Mouse Spinal Cord ◽  
Spinal Motor ◽  
Mature Mouse

scholarly journals Enflurane Actions on Spinal Cords from Mice That Lack the β3Subunit of the GABAAReceptor

2001 ◽  
Vol 95 (1) ◽  
pp. 154-164 ◽  
Author(s):  
Shirley M. E. Wong ◽  
Gong Cheng ◽  
Gregg E. Homanics ◽  
Joan J. Kendig
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Dominant Role ◽  
Glycine Receptor ◽  
Excitatory Postsynaptic Potential ◽  
Evoked Responses ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Root Potential ◽  
Beta3 Subunit

Background Gamma-aminobutyric acid type A (GABA(A)) receptors are considered important in mediating anesthetic actions. Mice lacking the beta3 subunit of this receptor (beta3-/-) have a higher enflurane minimum alveolar concentration (MAC) than wild types (+/+). MAC is predominantly determined in spinal cord. Methods The authors measured three population-evoked responses in whole spinal cords, namely, the excitatory postsynaptic potential (pEPSP), the slow ventral root potential (sVRP), and the dorsal root potential. Synaptic and glutamate-evoked currents from motor neurons in spinal cord slices were also measured. Results Sensitivity of evoked responses to enflurane did not differ between +/+ and -/- cords. The GABA(A) receptor antagonist bicuculline significantly (P < 0.05) attenuated the depressant effects of enflurane on pEPSP, sVRP and glutamate-evoked currents in +/+ but not -/- cords. The glycine antagonist strychnine elevated the pEPSP to a significantly greater extent in -/- than in +/+ cords, but the interactions between strychnine and enflurane did not differ between -/- and +/+ cords. Conclusions Similar enflurane sensitivity in spinal cords from -/- and +/+ mice was coupled with a decreased role for GABA(A) receptors in mediating the actions of enflurane in the former. This finding implies that other anesthetic targets substitute for GABA(A) receptors. Increase in glycine receptor-mediated inhibition was found in -/- cords, but the glycine receptor does not appear to be a substitute anesthetic target. This mutation thus led to a quantitative change in the molecular basis for anesthetic depression of spinal neurotransmission in a fashion not predicted by the mutation itself. The results argue against an immutable dominant role for GABA(A) receptors in mediating spinal contributions to MAC.

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