Transition from GABAergic to glycinergic synaptic transmission in newly formed spinal networks

The role of glycinergic and GABAergic systems in mediating spontaneous syna ptic transmission in newly formed neural networks was examined in motoneuro ns in the developing rat spinal cord. Properties of action potential-indepe ndent miniature inhibitory postsynaptic currents (mIPSCs) mediated by glyci ne and GABA(A) receptors (GlyR and GABA(A)R) were studied in spinal cord sl ices of 17- to 18-day-old embryos (E17-18) and 1- to 3-day-old postnatal ra ts (P1-3). mIPSC frequency and amplitude significantly increased after birt h, while their decay time decreased. To determine the contribution of glyci nergic and GABAergic synapses to those changes, GlyR- and GABA(A)R-mediated mIPSCs were isolated based on their pharmacological properties. Two popula tions of pharmacologically distinct mIPSCs were recorded in the presence of glycine or GABA(A) receptors antagonists: bicuculline-resistant, fast-deca ying GlyR-mediated mIPSCs, and strychnine-resistant, slow-decaying GABA(A)R -mediated mIPSCs. The frequency of GABA(A)R-mediated mIPSCs was fourfold hi gher than that of GlyR- mediated mIPSCs at E17-18, indicating that GABAergi c synaptic sites were functionally dominant at early stages of neural netwo rk formation. Properties of GABA(A)R-mediated mIPSC amplitude fluctuations changed from primarily unimodal skewed distribution at E17-18 to Gaussian m ixtures with two to three discrete components at P1-3. A developmental shif t from primarily long-duration GABAergic mIPSCs to short-duration glycinerg ic mIPSCs was evident after birth, when the frequency of GlyR- mediated mIP SCs increased 10-fold. This finding suggested that either the number of gly cinergic synapses or the probability of vesicular glycine release increased during the period studied. The increased frequency of GlyR- mediated mIPSC s was associated with more than a twofold increase in their mean amplitude, and in the number of motoneurons in which mIPSC amplitude fluctuations wer e best fitted by multi-component Gaussian curves. A third subpopulation of mIPSCs was apparent in the absence of glycine and GABA(A) receptor antagoni sts: mIPSCs with both fast and slow decaying components. Based on their dua l-component decay time and their suppression by either strychnine or bicucu lline, we assumed that these were generated by the activation of co-localiz ed postsynaptic glycine and GABA(A) receptors. The contribution of mixed gl ycine-GABA synaptic sites to the generation of mIPSCs did not change after birth. The developmental switch from predominantly long-duration GABAergic inhibitory synaptic currents to short-duration glycinergic currents might s erve as a mechanism regulating neuronal excitation in the developing spinal networks.