Production of 5 alpha -Reduced Neurosteroids Is Developmentally Regulated and Shapes GABA sub(A) Miniature IPSCs in Lamina II of the Spinal Cord

Production of 5 alpha -Reduced Neurosteroids Is Developmentally Regulated and Shapes GABA sub(A) Miniature IPSCs in Lamina II of the Spinal Cord

In lamina II of the spinal dorsal horn, synaptic inhibition mediated by ionotropic GABA sub(A) and glycine receptors contributes to the integration of peripheral nociceptive messages. Whole-cell patch-clamp recordings were performed from lamina II neurons in spinal cord slices to study the propertie...

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Veröffentlicht in:The Journal of neuroscience 2004-01, Vol.24 (4), p.907-915
Hauptverfasser: Keller, A F, Breton, J-D, Schlichter, R, Poisbeau, P
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container_title The Journal of neuroscience
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creator Keller, A F
Breton, J-D
Schlichter, R
Poisbeau, P
description In lamina II of the spinal dorsal horn, synaptic inhibition mediated by ionotropic GABA sub(A) and glycine receptors contributes to the integration of peripheral nociceptive messages. Whole-cell patch-clamp recordings were performed from lamina II neurons in spinal cord slices to study the properties of miniature IPSCs (mIPSCs) mediated by activation of GABA sub(A) and glycine receptors in immature (
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Whole-cell patch-clamp recordings were performed from lamina II neurons in spinal cord slices to study the properties of miniature IPSCs (mIPSCs) mediated by activation of GABA sub(A) and glycine receptors in immature (&lt;30 d) and adult rats. Blockade of neurosteroidogenesis by 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195), an inhibitor of the peripheral benzodiazepine receptor (PBR), or finasteride, which blocks 5 alpha -reductase, accelerated the decay kinetics of GABA sub(A) receptor-mediated mIPSCs in immature, but not in adult animals. Glycine receptor-mediated mIPSCs remained unaffected under these conditions. These results suggest the presence of a tonic production of 5 alpha -reduced neurosteroids in young rats that confers slow decay kinetics to GABA sub(A) mIPSCs. At all of the ages, selective stimulation of PBR by diazepam in the presence of flumazenil prolonged GABA sub(A) mIPSCs in a PK11195- and finasteride-sensitive manner. This condition also increased the proportion of mixed GABA sub(A)/glycine mIPSCs in the immature animals and led to the reappearance of mixed GABA sub(A)/glycine mIPSCs in the adult. 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title Production of 5 alpha -Reduced Neurosteroids Is Developmentally Regulated and Shapes GABA sub(A) Miniature IPSCs in Lamina II of the Spinal Cord
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