An ultrastructural study of the glycine transporter GLYT2 and its association with glycine in the superficial laminae of the rat spinal dorsal horn

Spike, Rosemary C.; Watt, Christine; Zafra, Francisco; Todd, Andrew

doi:10.1016/s0306-4522(96)00501-5

Cited by 88 publications

(68 citation statements)

References 32 publications

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“…35,36,58 -62 In contrast to GlyT2, GlyT1 is an astroglial glycine transporter. 60,61 Although immunoreactivity against the neuronal GlyT2 isoform is a reliable marker for glycinergic neurons, 34 GlyT2 antibody labels primarily axon terminals 35 and thus does not allow visualization of the cell bodies of glycinergic neurons for counting. Two forms of GAD, GAD65, and GAD67, responsible for synthesis of the inhibitory transmitter GABA, have been identified in vertebrates and mark GABAergic neurons.…”

Section: Discussionmentioning

confidence: 99%

Glycinergic Innervation of Motoneurons Is Deficient in Amyotrophic Lateral Sclerosis Mice

Chang

Martin

2009

The American Journal of Pathology

108

138

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Altered motoneuron excitability is involved in amyotrophic lateral sclerosis pathobiology. To test the hypothesis that inhibitory interneuron innervation of spinal motoneurons is abnormal in an amyotrophic lateral sclerosis mouse model, we measured GABAergic, glycinergic, and cholinergic immunoreactive terminals on spinal motoneurons in mice expressing a mutant form of human superoxide dismutase-1 with a Gly933 Ala substitution (G93A-SOD1) and in controls at different ages. Glutamic acid decarboxylase, glycine transporter-2, and choline acetyltransferase were used as markers for GABAergic, glycinergic, and cholinergic terminals, respectively. Triple immunofluorescent labeling of boutons contacting motoneurons was visualized by confocal microscopy and analyzed quantitatively. Glycine transporter-2-bouton density on lateral motoneurons was decreased significantly in G93A-SOD1 mice compared with controls. This reduction was absent at 6 weeks of age but present in asymptomatic 8-week-old mice and worsened with disease progression from 12 to 14 weeks of age. Motoneurons lost most glycinergic innervation by 16 weeks of age (end-stage) when there was a significant decrease in the numbers of motoneurons and choline acetyltransferase-positive boutons. No significant differences in glutamic acid decarboxylase-bouton densities were found in G93A-SOD1 mice. Reduction of glycinergic innervation preceded mitochondrial swelling and vacuolization. Calbindin-positive Renshaw cell number was decreased significantly at 12 weeks of age in G93A-SOD1 mice. Thus, either the selective loss of inhibitory glycinergic regulation of motoneuron function or glycinergic interneuron degeneration contributes to motoneuron degeneration in amyotrophic lateral sclerosis. (Am J

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Section: Discussionmentioning

confidence: 99%

Glycinergic Innervation of Motoneurons Is Deficient in Amyotrophic Lateral Sclerosis Mice

Chang

Martin

2009

The American Journal of Pathology

108

138

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“…Axon terminals of the other eight cells were immunoreactive for GlyT2 or were apposed to gephyrin and were therefore glycinergic (Table 2, cells 6 -13). Figure 3B illustrates axonal swellings from a labeled interneuron (Table 2, cell 7) that displayed the characteristic ring-like immunoreactivity for GlyT2 (Spike et al, 1997), whereas Figure 4 B shows gephyrin labeling associated with terminals from another cell (Table 2, cell 9) that was prepared for combined light and electron microscopy. Neither of these cells nor any of the others identified as glycinergic had axons that were immunoreactive for VGLUT1, VGLUT2,or GAD (Figs.…”

Section: Transmitter Content Of Terminals Location and Inputmentioning

confidence: 99%

Differential Projections of Excitatory and Inhibitory Dorsal Horn Interneurons Relaying Information from Group II Muscle Afferents in the Cat Spinal Cord

Bannatyne¹,

Edgley²,

Hammar³

et al. 2006

J. Neurosci.

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Dorsal horn interneurons with input from group II muscle spindle afferents are components of networks involved in motor control. Thirteen dorsal horn interneurons with monosynaptic group II input were characterized electrophysiologically and labeled intracellularly with Neurobiotin. Their axonal projections were traced, and neurotransmitter content was established by using immunocytochemistry. Two subpopulations were identified: five interneurons had axons that contained vesicular glutamate transporter 2 and hence were glutamatergic and excitatory. Terminals of the remaining eight interneurons were immunoreactive for the glycine transporter 2 or were apposed to gephyrin but did not contain the GABA-synthesizing enzyme glutamic acid decarboxylase and were therefore glycinergic and inhibitory. Excitatory cells were located mainly in the central region of lamina IV and had relatively small somata and restricted dendritic trees. In contrast, inhibitory interneurons were located more ventrally, in lamina V and had relatively larger somata and more extensive dendritic trees. Axonal projections of the two subpopulations differed considerably. Excitatory interneurons predominantly projected ipsilaterally, whereas most inhibitory interneurons projected both ipsilaterally and contralaterally. Three inhibitory axons formed contacts with large cholinergic cells in motor nuclei, thus revealing a novel direct coupling between inhibitory dorsal horn interneurons and motoneurons. The organization of the excitatory interneurons is consistent with current knowledge of reflex pathways to motoneurons, but the existence and connections of the inhibitory subpopulation could not be predicted from previous data. Our results indicate that these latter interneurons exercise widespread inhibitory control over a variety of cell types located on both sides of the spinal cord.

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“…In the adult spinal cord, immunoreactivity levels for GABA or GAD enzymes in neuronal somata are frequently unreliable for unequivocal detection of neurotransmitter phenotypes (Tran et al, 2003). Similarly the optimal indicators of glutamatergic and glycinergic phenotypes are the vesicular glutamate transporters (VGluTs) Oliveira et al, 2003;Alvarez et al, 2004) and the glycine transporter GlyT2 (Zafra et al, 1995;Spike et al, 1997), and these transporters are largely restricted to axonal varicosities. We therefore analyzed the neurotransmitter phenotype of adult V1-derived neurons by examining at high magnifications their EGFP-labeled axonal varicosities.…”

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confidence: 99%

Postnatal phenotype and localization of spinal cord V1 derived interneurons

Álvarez

Jonas

Sapir

et al. 2005

J of Comparative Neurology

220

284

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Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little however is known about their adult phenotypes. In order to further characterize interneuron cell types in the adult, the location, neurotransmitter phenotype, calciumbuffering protein expression and axon distributions of V1-derived neurons in the mouse spinal cord was determined. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons and the most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1-axons do not cross the midline. V1 derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons and other unidentified proprioceptive interneurons.Keywords inhibitory interneurons; engrailed-1; motor control; GABA; glycine; calbindin; parvalbumin; calretinin; motoneurons; ventral horn; spinal cord; development; V1 During the past 50 years, classical studies in the spinal cord have uncovered a wealth of details about the organization of interneuronal networks that control motoneuron firing, segmental reflexes and generate locomotor patterns in mammals (Jankowska et al., 1992). These studies, which relied heavily on the physiological identification of synaptic inputs and (Renshaw 1946;Eccles et al., 1954). IaINs are characterized by inputs from sensory Ia muscle afferents, provide reciprocal inhibition to antagonistic motor pools (Eccles et al., 1956) and are modulated by RCs (Hultborn et al., 1971). Despite enormous progress in further identification of interneurons using these methods, much is unknown and this approach is not without limitations (Edgley, 2001;Jankowska, 2001). Thus a comprehensive classification of ventral interneurons into major subclasses has not yet emerged.Recent studies indicate that distinct cell types in the adult spinal cord are derived from genetically-discrete populations of embryonic neurons (Jessell, 2000;Briscoe and Ericson, 2001;Lee and Pfaff, 2001;Goulding et al., 2002, Sa...

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An ultrastructural study of the glycine transporter GLYT2 and its association with glycine in the superficial laminae of the rat spinal dorsal horn

Cited by 88 publications

References 32 publications

Glycinergic Innervation of Motoneurons Is Deficient in Amyotrophic Lateral Sclerosis Mice

Glycinergic Innervation of Motoneurons Is Deficient in Amyotrophic Lateral Sclerosis Mice

Differential Projections of Excitatory and Inhibitory Dorsal Horn Interneurons Relaying Information from Group II Muscle Afferents in the Cat Spinal Cord

Postnatal phenotype and localization of spinal cord V1 derived interneurons

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