Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo

Neurotransmission during development regulates synaptic maturation in neural circuits, but the contribution of different neurotransmitter systems is unclear. We investigated the role of GABA(A) receptor-mediated Cl- conductances in the development of synaptic responses in the Xenopus visual system. Intracellular Cl- concentration ([Cl-](i)) was found to be high in immature tectal neurons and then falls over a period of several weeks. GABAergic synapses are present at early stages of tectal development and, when activated by optic nerve stimulation or visual stimuli, induce sustained depolarizing Cl- conductances that facilitate retinotectal transmission by NMDA receptors. To test whether depolarizing GABAergic inputs cooperate with NMDA receptors during activity-dependent maturation of glutamatergic synapses, we prematurely reduced [Cl-](i) in tectal neurons in vivo by expressing the Cl- transporter KCC2. This blocked the normal developmental increase in AMPA receptor-mediated retinotectal transmission and increased GABAergic synaptic input to tectal neurons. Therefore, depolarizing GABAergic transmission plays a pivotal role in the maturation of excitatory transmission and controls the balance of excitation and inhibition in the developing retinotectal circuit.