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Calcium-activated nonspecific cation current and synaptic depression promote network-dependent burst oscillations.

Central pattern generators (CPGs) produce neural-motor rhythms that often depend on specialized cellular or synaptic properties such as pacemaker neurons or alternating phases of synaptic inhibition. Motivated by experimental evidence suggesting that activity in the mammalian respiratory CPG, the preBötzinger complex, does not require either of these components, we present and analyze a mathematical model demonstrating an unconventional mechanism of rhythm generation in which glutamatergic synapses and the short-term depression of excitatory transmission play key rhythmogenic roles. Recurrent synaptic excitation triggers postsynaptic Ca(2+)-activated nonspecific cation current (I(CAN)) to initiate a network-wide burst. Robust depolarization due to I(CAN) also causes voltage-dependent spike inactivation, which diminishes recurrent excitation and thus attenuates postsynaptic Ca(2+) accumulation. Consequently, activity-dependent outward currents-produced by Na/K ATPase pumps or other ionic mechanisms-can terminate the burst and cause a transient quiescent state in the network. The recovery of sporadic spiking activity rekindles excitatory interactions and initiates a new cycle. Because synaptic inputs gate postsynaptic burst-generating conductances, this rhythm-generating mechanism represents a new paradigm that can be dubbed a 'group pacemaker' in which the basic rhythmogenic unit encompasses a fully interdependent ensemble of synaptic and intrinsic components. This conceptual framework should be considered as an alternative to traditional models when analyzing CPGs for which mechanistic details have not yet been elucidated.

Pubmed ID: 19196976


  • Rubin JE
  • Hayes JA
  • Mendenhall JL
  • Del Negro CA


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

February 24, 2009

Associated Grants

  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Action Potentials
  • Calcium
  • Computer Simulation
  • Ion Channel Gating
  • Ion Channels
  • Sodium
  • Synapses