Differential Plasticity of the GABAergic and Glycinergic Synaptic Transmission to Rat Lumbar Motoneurons after Spinal Cord Injury

Maturation of inhibitory postsynaptic transmission onto motoneurons in the rat occurs during the perinatal period, a time window during which pathways arising from the brainstem reach the lumbar enlargement of the spinal cord. There is a developmental switch in miniature IPSCs (mIPSCs) from predominantly long-duration GABAergic to short-duration glycinergic events. We investigated the effects of a complete neonatal [postnatal day 0 (P0)] spinal cord transection (SCT) on the expression of Glycine and GABAA receptor subunits (GlyR and GABAAR subunits) in lumbar motoneurons. In control rats, the density of GlyR increased from P1 to P7 to reach a plateau, whereas that of GABAAR subunits dropped during the same period. In P7 animals with neonatal SCT (SCT-P7), the GlyR densities were unchanged compared with controls of the same age, while the developmental downregulation of GABAAR was prevented. Whole-cell patch-clamp recordings of mIPSCs performed in lumbar motoneurons at P7 revealed that the decay time constant of miniature IPSCs and the proportion of GABAergic events significantly increased after SCT. After daily injections of the 5-HT2R agonist DOI, GABAAR immunolabeling on SCT-P7 motoneurons dropped down to values reported in control-P7, while GlyR labeling remained stable. A SCT made at P5 significantly upregulated the expression of GABAAR 1 week later with little, if any, influence on GlyR. We conclude that the plasticity of GlyR is independent of supraspinal influences whereas that of GABAAR is markedly influenced by descending pathways, in particular serotoninergic projections.

• Publication year

  2010

• Venue

  Journal of Neuroscience

• Publication date

  2010-03-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.6310-09.2010PMID 20203195PMCID PMC6634110
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• GlyR plasticity is independent of supraspinal influences, whereas GABAA receptor subunit plasticity is strongly shaped by descending pathways, especially serotoninergic projections.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• A spinal cord transection performed at P5 upregulates GABAA receptor subunit expression one week later with little effect on GlyR.

  Confidence 0.92

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• Daily DOI treatment lowers GABAA receptor subunit immunolabeling in SCT-P7 motoneurons to control-P7 levels, while GlyR labeling remains stable.

  Confidence 0.94

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• At P7, spinal cord transection increases the decay time constant of miniature IPSCs and raises the proportion of GABAergic events recorded from lumbar motoneurons.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• After neonatal spinal cord transection at P0, GlyR density at P7 remains unchanged relative to age-matched controls, but the normal developmental downregulation of GABAA receptor subunits is prevented.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• In control rats, GlyR density rises from P1 to P7 and then plateaus, while GABAA receptor subunit density decreases over the same period in lumbar motoneurons.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review

• descending pathways

  neural pathway

  Supraspinal axonal inputs reaching the spinal cord and influencing motoneuron synaptic development.

  Aliases: supraspinal influences, descending inputs

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• doi

  compound, agonist

  A 5-HT2R agonist administered daily to test serotonergic modulation of receptor expression after spinal cord transection.

  Aliases: 5-HT2R agonist DOI, DOI treatment

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• gabaa receptor subunits

  receptor, molecular entity

  The subunits of GABAA receptors whose immunolabeling is used to track GABAergic inhibitory synaptic components in motoneurons.

  Aliases: GABAAR subunits, GABAA receptors

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• glyr

  receptor, molecular entity

  The glycine receptor subunit labeling measured in lumbar motoneurons as an index of glycinergic inhibitory synapses.

  Aliases: glycine receptor, glycine receptor subunits

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• lumbar motoneurons

  cell type

  Motoneurons in the lumbar enlargement of the spinal cord that are examined for inhibitory synaptic receptor expression and transmission.

  Aliases: motoneurons, lumbar motor neurons

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• miniature ipscs

  electrophysiology measure, signal

  Spontaneous inhibitory postsynaptic currents recorded in motoneurons with whole-cell patch clamp.

  Aliases: mIPSCs, miniature inhibitory postsynaptic currents

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• serotoninergic projections

  neural pathway

  Descending serotonergic axonal projections implicated in modulating GABAA receptor plasticity in the spinal cord.

  Aliases: serotonergic projections, serotonin projections

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review
• spinal cord transection

  injury, procedure

  A complete neonatal lesion of the spinal cord used to interrupt descending inputs to the lumbar cord.

  Aliases: SCT, neonatal SCT

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) review

• Changes in GABA(A) receptor subunit gamma 2 in extensor and flexor motoneurons and astrocytes after spinal cord transection and motor training.

  2009cited by this paper
• Developmental up-regulation of the potassium-chloride cotransporter type 2 in the rat lumbar spinal cord.

  2009cited by this paper
• Strategies to restore motor functions after spinal cord injury.

  2009cited by this paper
• Intracellular Chloride Ions Regulate the Time Course of GABA-Mediated Inhibitory Synaptic Transmission

  2009cited by this paper
• High Intracellular Chloride Slows the Decay of Glycinergic Currents

  2008cited by this paper
• NKCC1 cotransporter inactivation underlies embryonic development of chloride‐mediated inhibition in mouse spinal motoneuron

  2008cited by this paper
• Plasticity of spinal cord locomotor networks and contribution of cation-chloride cotransporters.

  2008cited by this paper
• GABAA receptor subunit specificity: a tonic for the excited brain

  2008cited by this paper
• Dual personality of GABA/glycine-mediated depolarizations in immature spinal cord

  2007cited by this paper
• VGLUT1 and GLYT2 labeling of sacrocaudal motoneurons in the spinal cord injured spastic rat.

  2007cited by this paper
• Differential organization of γ‐aminobutyric acid type A and glycine receptors in the somatic and dendritic compartments of rat abducens motoneurons

  2007cited by this paper
• Acute Alterations of Glutamate, Glutamine, GABA, and Other Amino Acids After Spinal Cord Contusion in Rats

  2006cited by this paper
• Developmental dissociation of presynaptic inhibitory neurotransmitter and postsynaptic receptor clustering in the hypoglossal nucleus.

  2006cited by this paper
• Inhibitory postsynaptic potentials in lumbar motoneurons remain depolarizing after neonatal spinal cord transection in the rat.

  2006cited by this paper
• Differential expression of GABAA and glycine receptors in ALS‐resistant vs. ALS‐vulnerable motoneurons: possible implications for selective vulnerability of motoneurons

  2006cited by this paper
• Compensatory alteration of inhibitory synaptic circuits in cerebellum and thalamus of γ‐aminobutyric acid type A receptor α1 subunit knockout mice

  2006cited by this paper
• Immunofluorescence in brain sections: simultaneous detection of presynaptic and postsynaptic proteins in identified neurons

  2006cited by this paper
• Compensatory alteration of inhibitory synaptic circuits in cerebellum and thalamus of gamma-aminobutyric acid type A receptor alpha1 subunit knockout mice.

  2006cited by this paper
• A schizophrenia-related sensorimotor deficit links alpha 3-containing GABAA receptors to a dopamine hyperfunction.

  2005cited by this paper
• Ontogenic Changes of the Spinal GABAergic Cell Population Are Controlled by the Serotonin (5-HT) System: Implication of 5-HT1 Receptor Family

  2005cited by this paper
• Gephyrin Is Critical for Glycine Receptor Clustering But Not for the Formation of Functional GABAergic Synapses in Hippocampal Neurons

  2004cited by this paper
• Glutamate receptor subunit expression after spinal cord injury in young rats.

  2004cited by this paper
• Pre- and post-synaptic mechanisms regulating the clustering of type A gamma-aminobutyric acid receptors (GABAA receptors).

  2003cited by this paper
• Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality.

  2003cited by this paper
• Formation and plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications.

  2003influential reference
• Heterogeneous synaptic covering and differential charge transfer sensitivity among the dendrites of a reconstructed abducens motor neurone: Correlations between electron microscopic and computer simulation data

  2003cited by this paper
• Association of gephyrin and glycine receptors in the human brainstem and spinal cord: an immunohistochemical analysis.

  2003cited by this paper
• Reversible Disorganization of the Locomotor Pattern after Neonatal Spinal Cord Transection in the Rat

  2003influential reference
• Locomotor recovery in the chronic spinal rat: effects of long‐term treatment with a 5‐HT2 agonist

  2002cited by this paper
• Use-Dependent Modulation of Inhibitory Capacity in the Feline Lumbar Spinal Cord

  2002cited by this paper
• Postnatal expression of neurotransmitters, receptors, and cytochrome oxidase in the rat pre-Bötzinger complex.

  2002cited by this paper
• Contribution of the α1-GABAA receptor subtype to the pharmacological actions of benzodiazepine site inverse agonists

  2002cited by this paper
• Glycine and GABAA receptor subunits on Renshaw cells: Relationship with presynaptic neurotransmitters and postsynaptic gephyrin clusters

  2002cited by this paper
• Development of posture and locomotion: an interplay of endogenously generated activities and neurotrophic actions by descending pathways.

  2002cited by this paper
• Which GABA ,-receptor subtypes really occur in the brain ?

  2001influential reference
• Region-Specific Developmental Specialization of GABA–Glycine Cosynapses in Laminas I–II of the Rat Spinal Dorsal Horn

  2001cited by this paper
• The glycinergic inhibitory synapse

  2001influential reference
• Transition from GABAergic to glycinergic synaptic transmission in newly formed spinal networks.

  2001cited by this paper
• Retraining the injured spinal cord

  2001cited by this paper
• Gephyrin, a major postsynaptic protein of GABAergic synapses

  2000cited by this paper
• Differential maturation of motoneurons innervating ankle flexor and extensor muscles in the neonatal rat

  2000cited by this paper
• Developmental change of GABA(A) receptor-mediated current in rat hippocampus.

  2000cited by this paper
• Reduced synaptic clustering of GABA and glycine receptors in the retina of the gephyrin null mutant mouse

  2000cited by this paper
• An immunogold investigation of the relationship between the amino acids GABA and glycine and their transporters in terminals in the guinea-pig anteroventral cochlear nucleus.

  2000cited by this paper
• Direct Agonists for Serotonin Receptors Enhance Locomotor Function in Rats that Received Neural Transplants after Neonatal Spinal Transection

  1999influential reference
• Junctional versus Extrajunctional Glycine and GABAAReceptor-Mediated IPSCs in Identified Lamina I Neurons of the Adult Rat Spinal Cord

  1999cited by this paper
• Loss of Postsynaptic GABAA Receptor Clustering in Gephyrin-Deficient Mice

  1999cited by this paper
• Transplantation of embryonic Raphe cells regulates the modifications of the gabaergic phenotype occurring in the injured spinal cord.

  1999cited by this paper
• GABA(A) receptor-mediated miniature postsynaptic currents and alpha-subunit expression in developing cortical neurons.

  1999cited by this paper
• Corelease of two fast neurotransmitters at a central synapse.

  1998cited by this paper
• Development of spontaneous synaptic transmission in the rat spinal cord.

  1998cited by this paper
• Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo.

  1998cited by this paper
• Physiological functions of GABA-induced depolarizations in the developing rat spinal cord.

  1998cited by this paper
• The glycine transporter GLYT2 is a reliable marker for glycine-immunoreactive neurons.

  1997cited by this paper
• The Projections to the Spinal Cord of the Rat During Development: A Timetable of Descent

  1997cited by this paper
• An ultrastructural study of the glycine transporter GLYT2 and its association with glycine in the superficial laminae of the rat spinal dorsal horn.

  1997cited by this paper
• Modulation of GABAA receptor function by G protein-coupled 5-HT2C receptors.

  1996cited by this paper
• Distribution of immunoreactivity for the beta 2 and beta 3 subunits of the GABAA receptor in the mammalian spinal cord.

  1996influential reference
• Restoration of extensor excitability in the acute spinal cat by the 5-HT2 agonist DOI.

  1996cited by this paper
• Laminar compartmentalization of GABAA-receptor subtypes in the spinal cord: an immunohistochemical study

  1996cited by this paper
• Distribution of immunoreactivity for the β2 and β3 subunits of the GABAA receptor in the mammalian spinal cord

  1996cited by this paper
• Regional Distribution and Developmental Variation of the Glycine Transporters GLYT1 and GLYT2 in the Rat CNS

  1995cited by this paper
• Development of glycine- and GABA-gated currents in rat spinal motoneurons.

  1995cited by this paper
• GABAA‐receptor heterogeneity in the adult rat brain: Differential regional and cellular distribution of seven major subunits

  1995cited by this paper
• Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors.

  1995cited by this paper
• Dependence of the GABAA receptor gating kinetics on the alpha‐subunit isoform: implications for structure‐function relations and synaptic transmission.

  1995cited by this paper
• Immunohistochemical evidence for coexistence of glycine and GABA in nerve terminals on cat spinal motoneurones: an ultrastructural study.

  1994cited by this paper
• GABA and glycine frequently colocalize in terminals on cat spinal motoneurons

  1994cited by this paper
• Spatial integration of local transmitter responses in motoneurones of the turtle spinal cord in vitro.

  1994cited by this paper
• Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study

  1994influential reference
• Distribution of Gephyrin Transcripts in the Adult and Developing Rat Brain

  1993cited by this paper
• Ontogeny of GABAA receptor subunit mRNAs in rat spinal cord and dorsal root ganglia

  1993cited by this paper
• Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels.

  1992cited by this paper
• Early development of glycine- and GABA-mediated synapses in rat spinal cord

  1992cited by this paper
• Distribution of GABAA receptor subunit mRNAs in rat lumbar spinal cord.

  1991cited by this paper
• Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain.

  1991cited by this paper
• Mapping of antigenic epitopes on the alpha 1 subunit of the inhibitory glycine receptor.

  1991cited by this paper
• The effect of subunit composition of rat brain GABAA receptors on channel function.

  1990cited by this paper
• The effects of serotonergic drugs on the locomotor pattern and on cutaneous reflexes of the adult chronic spinal cat.

  1990cited by this paper
• Pre‐ and post‐natal ontogeny of serotonergic projections to the rat spinal cord

  1989cited by this paper
• Distribution of glycine receptors at central synapses: an immunoelectron microscopy study

  1985cited by this paper
• Monoclonal antibodies and peptide mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord.

  1984cited by this paper
• [Development of excitable membrane in an early embryo].

  1984cited by this paper
• Branching dendritic trees and motoneuron membrane resistivity.

  1959cited by this paper
• Dictionary of Statistical Terms.

  1958cited by this paper

• KCC2 phosphorylation dynamics relate to oligomerization during development and after spinal cord injury.

  2026cites this paper
• Transspinal stimulation preceding assisted step training reorganizes neuronal excitability and function of inhibitory networks in spinal cord injury: a randomized controlled trial

  2025cites this paper
• Calpains at the Crossroads of Spinal Cord Physiology, Plasticity, and Pathology

  2025cites this paper
• Plastic Events of the Vestibular Nucleus: the Initiation of Central Vestibular Compensation

  2024cites this paper
• Plasticity in Motoneurons Following Spinal Cord Injury in Fructose-induced Diabetic Rats

  2022cites this paper
• How Does the Central Nervous System for Posture and Locomotion Cope With Damage-Induced Neural Asymmetry?

  2022cites this paper
• Regulation of perineuronal net components in the synaptic bouton vicinity on lumbar α-motoneurons in the rat after spinalization and locomotor training: New insights from spatio-temporal changes in gene, protein expression and WFA labeling.

  2022cites this paper
• GABAergic Mechanisms Can Redress the Tilted Balance between Excitation and Inhibition in Damaged Spinal Networks

  2021cites this paper
• Deciphering Spinal Endogenous Dopaminergic Mechanisms That Modulate Micturition Reflexes in Rats with Spinal Cord Injury

  2021influential citation
• Alteration of glycinergic receptor expression in lumbar spinal motoneurons is involved in the mechanisms underlying spasticity after spinal cord injury.

  2020influential citation
• Role of chloride cotransporters in the development of spasticity and neuropathic pain after spinal cord injury

  2020cites this paper
• Differential effects of spinal cord transection on glycinergic and GABAergic synaptic signaling in sub-lesional lumbar motoneurons.

  2020cites this paper
• Locomotor central pattern generator excitability states and serotonin sensitivity after spontaneous recovery from a neonatal lumbar spinal cord injury.

  2019cites this paper
• Loss of inhibitory synapses causes locomotor network dysfunction of the rat spinal cord during prolonged maintenance in vitro.

  2019cites this paper
• Changes in innervation of lumbar motoneurons and organization of premotor network following training of transected adult rats

  2018cites this paper
• Biohybrid Membrane Systems for Testing Molecules and Stem Cell Therapy in Neuronal Tissue Engineering.

  2017cites this paper
• Cellular reactions and compensatory tissue re‐organization during spontaneous recovery after spinal cord injury in neonatal mice

  2017cites this paper
• Histamine 1 receptor-Gβγ-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock

  2016cites this paper
• A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function

  2016cites this paper
• BDNF Signaling Promotes Vestibular Compensation by Increasing Neurogenesis and Remodeling the Expression of Potassium-Chloride Cotransporter KCC2 and GABAA Receptor in the Vestibular Nuclei

  2016cites this paper
• Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury.

  2015cites this paper
• Serotonergic modulation of post-synaptic inhibition and locomotor alternating pattern in the spinal cord

  2014influential citation
• Inhibitory glycinergic neurotransmission in the mammalian auditory brainstem upon prolonged stimulation: short-term plasticity and synaptic reliability

  2014cites this paper
• The impact of discrete modes of spinal cord injury on bladder muscle contractility

  2013cites this paper
• Plastic changes in lumbar segments after thoracic spinal cord injuries in adult rats: An integrative view of spinal nociceptive dysfunctions

  2013influential citation
• A Neonatal Mouse Spinal Cord Injury Model for Assessing Post-Injury Adaptive Plasticity and Human Stem Cell Integration

  2013cites this paper
• Prenatal Exposure to Fenugreek Impairs Sensorimotor Development and the Operation of Spinal Cord Networks in Mice

  2013cites this paper
• Sodium-Mediated Plateau Potentials in Lumbar Motoneurons of Neonatal Rats

  2013cites this paper
• Transplantation of Human Umbilical Cord Blood or Amniotic Epithelial Stem Cells Alleviates Mechanical Allodynia after Spinal Cord Injury in Rats

  2013cites this paper
• Selective Effects of Baclofen on Use-Dependent Modulation of GABAB Inhibition after Tetraplegia

  2013cites this paper
• Maturation of Inhibitory Synaptic Transmission in the Spinal Cord: Role of the Brain Stem and Contribution to the Development of Motor Patterns

  2013cites this paper
• Wind-Up of Spinal Neurons Contributes To Supramaximal Volitional Torque in Human Spinal Cord Injury

  2012cites this paper
• Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

  2012cites this paper
• Timing of developmental sequences in different brain structures: physiological and pathological implications

  2012cites this paper
• Chapter 1--importance of chloride homeostasis in the operation of rhythmic motor networks.

  2011cites this paper
• Distinct α GABA(A)R subunits influence structural and transcriptional properties of CA1 hippocampal neurons.

  2011cites this paper
• Contribution of 5‐HT to locomotion – the paradox of Pet‐1−/− mice

  2011cites this paper
• The time course of serotonin 2A receptor expression after spinal transection of rats: an immunohistochemical study.

  2011cites this paper
• The time course of serotonin 2C receptor expression after spinal transection of rats: an immunohistochemical study.

  2011cites this paper
• Modulation of inhibitory strength and kinetics facilitates regulation of persistent inward currents and motoneuron excitability following spinal cord injury.

  2011influential citation
• The Animal Model of Spinal Cord Injury as an Experimental Pain Model

  2011cites this paper
• Cellular and axonal plasticity in the lesioned spinal cord of adult zebrafish

  2011cites this paper
• Characterization of last‐order premotor interneurons by transneuronal tracing with rabies virus in the neonatal mouse spinal cord

  2011cites this paper
• The developmental regulation of local and descending control of dorsal horn neurons in the rat

  2010cites this paper