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The Journal of Neuroscience, November 15, 2001, 21(22):8966-8978
The Role of Activity-Dependent Network Depression in the
Expression and Self-Regulation of Spontaneous Activity in the
Developing Spinal Cord
Joël
Tabak1,
John
Rinzel2, and
Michael J.
O'Donovan1
1 Laboratory of Neural Control, Section on
Developmental Neurobiology, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
20892, and 2 Center for Neural Science and Courant
Institute of Mathematical Sciences, New York University, New York, New
York, 10003
Spontaneous episodic activity occurs throughout the developing
nervous system 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 generation 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 positive correlation
between episode duration and the preceding inter-episode interval, but
not with the following interval, suggesting that episode onset is
stochastic whereas episode termination occurs deterministically, when
network excitability falls to a fixed level. This is true over a wide
range of developmental stages and under blockade of glutamatergic or
GABAergic/glycinergic synapses.
We also demonstrate that during glutamatergic blockade the
remaining part of the network becomes more excitable, compensating for
the loss of glutamatergic synapses and allowing spontaneous activity to
recover. This compensatory increase in the excitability of the
remaining network reflects the progressive increase in synaptic
efficacy that occurs in the absence of activity. Therefore, the
mechanism responsible for the episodic nature of the activity automatically renders this activity robust to network disruptions. The
results are presented using the framework of our computational model of
spontaneous activity in the developing cord. Specifically, we show how
they follow logically from a bistable network with a slow
activity-dependent depression switching periodically between the
active and inactive states.
Key words:
spontaneous activity; activity-dependent depression; network plasticity; homeostasis; spinal cord; chick embryo
Copyright © 2001 Society for Neuroscience 0270-6474/01/21228966-13$05.00/0
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