Homeostatic regulation of intrinsic excitability and synaptic transmission in a developing visual circuit.

One of the major challenges faced by the developing visual system is how to stably process visual information, yet at the same time remain flexible enough to accommodate growth and plasticity induced by visual experience. We find that in the Xenopus retinotectal circuit, during a period in development when the retinotectal map undergoes activity-dependent refinement and visual inputs strengthen, tectal neurons adapt their intrinsic excitability such that a stable relationship between the total level of synaptic input and tectal neuron spike output is conserved. This homeostatic balance between synaptic and intrinsic properties is maintained, in part, via regulation of voltage-gated Na+ currents, resulting in a stable neuronal input-output function. We experimentally manipulated intrinsic excitability or synapse strengthening in developing tectal neurons in vivo by electroporation of a leak K+ channel gene or a peptide that interferes with normal AMPA receptor trafficking. Both manipulations resulted in a compensatory increase in voltage-gated Na+ currents. This suggests that intrinsic neuronal properties are actively regulated as a function of the total level of neuronal activity experienced during development. We conclude that the coordinated changes between synaptic and intrinsic properties allow developing optic tectal neurons to remain within a stable dynamic range, even as the pattern and strength of visual inputs changes over development, suggesting that homeostatic regulation of intrinsic properties plays a central role in the functional development of neural circuits.