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Maturation of the GABAergic transmission in normal and pathologic motoneurons.

Allain AE, Le Corronc H, Delpy A, Cazenave W, Meyrand P, Legendre P, Branchereau P - Neural Plast. (2011)

Bottom Line: γ-aminobutyric acid (GABA) acting on Cl(-)-permeable ionotropic type A (GABA(A)) receptors (GABA(A)R) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates.In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor.In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABA(A)R subunits.

View Article: PubMed Central - PubMed

Affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux et CNRS-UMR 5287, avenue des Facultés, 4ème étage Est, 33405 Talence, France.

ABSTRACT
γ-aminobutyric acid (GABA) acting on Cl(-)-permeable ionotropic type A (GABA(A)) receptors (GABA(A)R) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates. In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor. In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABA(A)R subunits. We finally discuss the role of GABA and its GABA(A)R in immature hypoglossal motoneurons of the spastic (SPA) mouse, a model of human hyperekplexic syndrome.

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(a) Developmental changes in the proportions of GABAergic and glycinergic synaptic activity in various areas of the central nervous system.  (b) Examples of individual glycinergic (left) GABAergic (middle) and mixed (right) miniature inhibitory postsynaptic currents (mIPSCs) recorded in a hypoglossal motoneuron at P15, in the presence of tetrodotoxin (a blocker of voltage-gated sodium channels). Note the slower decay phase of the GABAergic mIPSC compared to the glycinergic mIPSC. Decay phase of GABAergic and glycinergic events is better fitted with a single exponential function, while a double exponential function is required to fit the decay phase of mixed events. (c) Relative proportions of glycinergic, GABAergic and mixed mIPSCs at P3–P5 (black bars) and at P15 (white bars) in wild-type mice. (d) Relative proportions of glycinergic, GABAergic and mixed miniature postsynaptic events at P5–P7 (black bars) and at P15–P18 (white bars) in SPA mice. (Adapted from    [118, 126]).
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fig2: (a) Developmental changes in the proportions of GABAergic and glycinergic synaptic activity in various areas of the central nervous system. (b) Examples of individual glycinergic (left) GABAergic (middle) and mixed (right) miniature inhibitory postsynaptic currents (mIPSCs) recorded in a hypoglossal motoneuron at P15, in the presence of tetrodotoxin (a blocker of voltage-gated sodium channels). Note the slower decay phase of the GABAergic mIPSC compared to the glycinergic mIPSC. Decay phase of GABAergic and glycinergic events is better fitted with a single exponential function, while a double exponential function is required to fit the decay phase of mixed events. (c) Relative proportions of glycinergic, GABAergic and mixed mIPSCs at P3–P5 (black bars) and at P15 (white bars) in wild-type mice. (d) Relative proportions of glycinergic, GABAergic and mixed miniature postsynaptic events at P5–P7 (black bars) and at P15–P18 (white bars) in SPA mice. (Adapted from [118, 126]).

Mentions: During the first 3 weeks of rodent postnatal development, inhibitory synaptic transmission changes in multiple ways that differ depending on brain areas. Electrophysiology and immunocytochemistry suggest that the respective contribution of the glycinergic and GABAergic transmission to the overall inhibitory message received by postsynaptic neurons may vary during the developmental period. For example, a developmental switch from a predominant GABAergic to main glycinergic neurotransmission occurs in the lumbar spinal cord [69] and in the lateral superior olive of young rodents [108, 109], while GABAergic neurotransmission dominates in developing collicular neurons [110] (Figure 2(a)).


Maturation of the GABAergic transmission in normal and pathologic motoneurons.

Allain AE, Le Corronc H, Delpy A, Cazenave W, Meyrand P, Legendre P, Branchereau P - Neural Plast. (2011)

(a) Developmental changes in the proportions of GABAergic and glycinergic synaptic activity in various areas of the central nervous system.  (b) Examples of individual glycinergic (left) GABAergic (middle) and mixed (right) miniature inhibitory postsynaptic currents (mIPSCs) recorded in a hypoglossal motoneuron at P15, in the presence of tetrodotoxin (a blocker of voltage-gated sodium channels). Note the slower decay phase of the GABAergic mIPSC compared to the glycinergic mIPSC. Decay phase of GABAergic and glycinergic events is better fitted with a single exponential function, while a double exponential function is required to fit the decay phase of mixed events. (c) Relative proportions of glycinergic, GABAergic and mixed mIPSCs at P3–P5 (black bars) and at P15 (white bars) in wild-type mice. (d) Relative proportions of glycinergic, GABAergic and mixed miniature postsynaptic events at P5–P7 (black bars) and at P15–P18 (white bars) in SPA mice. (Adapted from    [118, 126]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3140191&req=5

fig2: (a) Developmental changes in the proportions of GABAergic and glycinergic synaptic activity in various areas of the central nervous system. (b) Examples of individual glycinergic (left) GABAergic (middle) and mixed (right) miniature inhibitory postsynaptic currents (mIPSCs) recorded in a hypoglossal motoneuron at P15, in the presence of tetrodotoxin (a blocker of voltage-gated sodium channels). Note the slower decay phase of the GABAergic mIPSC compared to the glycinergic mIPSC. Decay phase of GABAergic and glycinergic events is better fitted with a single exponential function, while a double exponential function is required to fit the decay phase of mixed events. (c) Relative proportions of glycinergic, GABAergic and mixed mIPSCs at P3–P5 (black bars) and at P15 (white bars) in wild-type mice. (d) Relative proportions of glycinergic, GABAergic and mixed miniature postsynaptic events at P5–P7 (black bars) and at P15–P18 (white bars) in SPA mice. (Adapted from [118, 126]).
Mentions: During the first 3 weeks of rodent postnatal development, inhibitory synaptic transmission changes in multiple ways that differ depending on brain areas. Electrophysiology and immunocytochemistry suggest that the respective contribution of the glycinergic and GABAergic transmission to the overall inhibitory message received by postsynaptic neurons may vary during the developmental period. For example, a developmental switch from a predominant GABAergic to main glycinergic neurotransmission occurs in the lumbar spinal cord [69] and in the lateral superior olive of young rodents [108, 109], while GABAergic neurotransmission dominates in developing collicular neurons [110] (Figure 2(a)).

Bottom Line: γ-aminobutyric acid (GABA) acting on Cl(-)-permeable ionotropic type A (GABA(A)) receptors (GABA(A)R) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates.In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor.In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABA(A)R subunits.

View Article: PubMed Central - PubMed

Affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux et CNRS-UMR 5287, avenue des Facultés, 4ème étage Est, 33405 Talence, France.

ABSTRACT
γ-aminobutyric acid (GABA) acting on Cl(-)-permeable ionotropic type A (GABA(A)) receptors (GABA(A)R) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates. In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor. In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABA(A)R subunits. We finally discuss the role of GABA and its GABA(A)R in immature hypoglossal motoneurons of the spastic (SPA) mouse, a model of human hyperekplexic syndrome.

Show MeSH
Related in: MedlinePlus