title: Region-specific developmental specialization of GABA-glycine cosynapses in laminas I-II of the rat spinal dorsal horn.
abstract: The spinal dorsal horn is the first level of the CNS in which nociceptive input from sensory afferents is integrated and transmitted. Although inhibitory control in this region has a crucial impact on pain transmission, the respective contribution of GABA and glycine to this inhibition remains elusive. We have previously documented co-release of GABA and glycine at the same inhibitory synapse in spinal laminas I-II of adult rats [older than postnatal day 30 (P30)]. However, despite this co-release, individual miniature inhibitory postsynaptic currents (mIPSCs) were mediated by either glycine receptors (GlyR) or GABA(A) receptors (GABA(A)R), yet never by the two together. In contrast, recent studies of ventral horn immature inhibitory synapses (</=P21) reported individual mIPSCs that were mediated by both GABA(A)Rs and GlyRs. This raises the question of whether mixed mIPSCs are present in immature lamina I-II neurons yet are lost through a maturation-dependent synaptic specialization. To test this, we recorded mIPSCs using patch-clamp techniques in lamina I-II neurons in spinal slices taken at different stages of development. We found that, in neurons younger than P23, both GlyR-only and GABA(A)R-only mIPSCs could be recorded, in addition to mixed GABA(A)R-GlyR mIPSCs. With maturation however, both lamina I-II neurons gradually discontinued exhibiting mixed mIPSCs, although with differing patterns of specialization. Yet, at all developmental stages, benzodiazepine administration could unmask mixed mIPSCs. Together, these findings indicate that, although GABA and glycine are continually co-released throughout development, junctional codetection ceases by adulthood. This indicates an age-dependent postsynaptic tuning of inhibitory synapses that occurs in a region-specific manner.
authors.affiliation: Laboratoire de Neurophysiologie Cellulaire et Intégrée, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7519, Université Louis Pasteur, 67084 Strasbourg cedex, France.
authors.forename: A F
authors.initials: AF
authors.lastname: Keller
authors.forename: J A
authors.initials: JA
authors.lastname: Coull
authors.forename: N
authors.initials: N
authors.lastname: Chery
authors.forename: P
authors.initials: P
authors.lastname: Poisbeau
authors.forename: Y
authors.initials: Y
authors.lastname: De Koninck
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018757:GABA Modulators; D012430:Ruthenium Red; D005680:gamma-Aminobutyric Acid; D005998:Glycine