Region-specific developmental specialization of GABA-glycine cosynapses inlaminas I-II of the rat spinal dorsal horn

The spinal dorsal horn is the first level of the CNS in which nociceptive i nput from sensory afferents is integrated and transmitted. Although inhibit ory control in this region has a crucial impact on pain transmission, the r espective contribution of GABA and glycine to this inhibition remains elusi ve. We have previously documented co-release of GABA and glycine at the sam e inhibitory synapse in spinal laminas I-II of adult rats [older than postn atal day 30 (P30)]. However, despite this co-release, individual miniature inhibitory postsynaptic currents (mIPSCs) were mediated by either glycine r eceptors (GlyR) or GABA(A) receptors (GABA(A)R), yet never by the two toget her. In contrast, recent studies of ventral horn immature inhibitory synaps es (less than or equal to P21) reported individual mIPSCs that were mediate d by both GABA(A)Rs and GlyRs. This raises the question of whether mixed mI PSCs are present in immature lamina I-II neurons yet are lost through a mat uration-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 additio n to mixed GABA(A)R-GlyR mIPSCs. With maturation however, both lamina I-II neurons gradually discontinued exhibiting mixed mIPSCs, although with diffe ring patterns of specialization. Yet, at all developmental stages, benzodia zepine administration could unmask mixed mIPSCs. Together, these findings i ndicate that, although GABA and glycine are continually co-released through out development, junctional codetection ceases by adulthood. This indicates an age-dependent postsynaptic tuning of inhibitory synapses that occurs in a region-specific manner.