Dynamics of excitatory synaptic components in sustained firing at low rates.
Sustained firing is necessary for the persistent activity associated with working memory. The relative contributions of the reverberation of excitation and of the temporal dynamics of the excitatory postsynaptic potential (EPSP) to the maintenance of activity are difficult to evaluate in classical preparations. We used simplified models of synchronous excitatory networks, hippocampal autapses and pairs, to study the synaptic mechanisms underlying firing at low rates. Calcium imaging and cell attached recordings showed that these neurons spontaneously fired bursts of action potentials that lasted for seconds over a wide range of frequencies. In 2-wk-old cells, the median firing frequency was low (11 +/- 8.8 Hz), whereas in 3- to 4-wk-old cells, it decreased to a very low value (2 +/- 1.3 Hz). In both cases, we have shown that the slowest synaptic component supported firing. In 2-wk-old autapses, antagonists of N-methyl-d-aspartate receptors (NMDARs) induced rare isolated spikes showing that the NMDA component of the EPSP was essential for bursts at low frequency. In 3- to 4-wk-old neurons, the very low frequency firing was maintained without the NMDAR activation. However EGTA-AM or alpha-methyl-4-carboxyphenylglycine (MCPG) removed the very slow depolarizing component of the EPSP and prevented the sustained firing at very low rate. A metabotropic glutamate receptor (mGluR)-activated calcium sensitive conductance is therefore responsible for a very slow synaptic component associated with firing at very low rate. In addition, our observations suggested that the asynchronous release of glutamate might participate also in the recurring bursting.
Wyart
Claire
C
Laboratoire de Dynamique des Fluides Complexes, Unité 7506 Centre National de la Recherche Scientifique, Université Louis Pasteur, Institut de Physique, Strasbourg, France.
Cocco
Simona
S
Bourdieu
Laurent
L
Léger
Jean-Francois
JF
Herr
Catherine
C
Chatenay
Didier
D
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D004533:Egtazic Acid; C046770:EGTA acetoxymethyl ester; D002118:Calcium