Development of GABAergic and glycinergic transmission in the neonatal rat dorsal horn

Cutaneous spinal sensory transmission appears to lack inhibitory control in the newborn spinal cord, but the properties of GABAergic and glycinergic synapses in the neonatal dorsal horn have not been characterized. Whole-cell patch-clamp recordings from rat superficial dorsal horn neurons in spinal cord slices at postnatal day 0 (P0) to P2, P6-P7, and P13-P14 revealed an age-dependent increase in the frequency of spontaneous IPSCs, which were abolished by the GABA(A) receptor (GABA(A)R) antagonist bicuculline between P0 and P7 but not at P14. GABA(A)R-mediated miniature IPSCs (mIPSCs), but not glycinergic mIPSCs, were present at birth, and GABA mIPSCs remained more frequent than glycine mIPSCs at all ages. Sciatic nerve stimulation resulted in IPSCs with both GABAergic and glycinergic components, although a larger contribution arose from GABA(A) receptors at all ages. In gramicidin perforated patch-clamp recordings, exogenous GABA applications produced depolarization in 40% of neurons at P0-P2, but the reversal potential of GABA-evoked currents (E(GABA)) was consistently more negative than action potential threshold at this age. By P6-P7, GABA evoked only membrane hyperpolarization. The GABA(B)R agonist baclofen elicited an outward current in all neurons with peak amplitudes observed by P6-P7 and abolished sciatic nerve-evoked monosynaptic glutamatergic EPSCs in all groups. The results show considerable postnatal development of inhibitory processing in the dorsal horn with GABAergic mechanisms initially dominant over glycinergic events. GABA(A)R-mediated depolarizations during the first postnatal week are likely to be important for the maturation of spinal networks but do not provide a major excitatory drive to the newborn dorsal horn.