The role of activity-dependent network depression in the expression and self-regulation of spontaneous activity in the developing spinal cord

Spontaneous episodic activity occurs throughout the developing nervous syst em because immature circuits are hyperexcitable. It is not fully understood how the temporal pattern of this activity is regulated. Here, we study the role of activity-dependent depression of network excitability in the gener ation and regulation of spontaneous activity in the embryonic chick spinal cord. We demonstrate that the duration of an episode of activity depends on the network excitability at the beginning of the episode. We found a posit ive correlation between episode duration and the preceding inter-episode in terval, but not with the following interval, suggesting that episode onset is stochastic whereas episode termination occurs deterministically, when ne twork excitability falls to a fixed level. This is true over a wide range o f developmental stages and under blockade of glutamatergic or GABAergic/gly cinergic synapses. We also demonstrate that during glutamatergic blockade the remaining part o f the network becomes more excitable, compensating for the loss of glutamat ergic synapses and allowing spontaneous activity to recover. This compensat ory increase in the excitability of the remaining network reflects the prog ressive increase in synaptic efficacy that occurs in the absence of activit y. Therefore, the mechanism responsible for the episodic nature of the acti vity automatically renders this activity robust to network disruptions. The results are presented using the framework of our computational model of sp ontaneous activity in the developing cord. Specifically, we show how they f ollow logically from a bistable network with a slow activity-dependent depr ession switching periodically between the active and inactive states.