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Cellular mechanisms underlying the rhythmic bursts induced by NMDA microiontophoresis at the apical dendrites of CA1 pyramidal neurons
Author(s) -
Bonansco Christian,
Buño Washington
Publication year - 2002
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.10067
Subject(s) - cnqx , chemistry , depolarization , nmda receptor , neuroscience , tetraethylammonium , biophysics , tetrodotoxin , afterhyperpolarization , bapta , bicuculline , intracellular , gabaa receptor , ampa receptor , receptor , biology , potassium , biochemistry , organic chemistry
Abstract This article reports the cellular mechanisms underlying a form of intracellular “theta‐like” (θ‐like) rhythm evoked in vitro by microiontophoresis of N‐methyl‐ D ‐aspartate (NMDA) at the apical dendrites of CA1 pyramidal neurons. Rhythmic membrane potential (Vm) oscillations and action potential (AP) bursts (≈6 Hz; ≈20 mV; ≈2–5 APs) were evoked in all cells. The response lasted ≈2 s, and the initial oscillations were usually small (<20 mV) and below AP threshold. Rhythmic bursts were never evoked by imposed depolarization in the absence of NMDA. Block of Na + conductance with tetrodotoxin (TTX) (1.5 μM), of non‐NMDA receptors with 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) (20 μM) and of synaptic inhibition by bicuculline (50 μM) and picrotoxin (50 μM) did not prevent NMDA oscillation. Inhibition of the voltage dependence of the NMDA conductance in Mg 2+ ‐free Ringer's solution blocked oscillations. Preventing Ca 2+ influx with Ca 2+ ‐free and Co 2+ (2‐mM) solutions and block of the slow Ca 2+ ‐dependent afterhyperpolarization (sAHP) by carbamilcholine (5 μM), isoproterenol (10 μM), and intracellular BAPTA blocked NMDA oscillations. Inhibition of L‐type Ca 2+ conductance with nifedipine (30 μM) reduced oscillation amplitude. Block of tetraethylammonium (TEA) (10 mM) and 4AP (10 mM)‐sensitive K + conductance increased the duration and amplitude, but not the frequency, of oscillations. In conclusion, θ‐like bursts relied on the voltage dependence of the NMDA conductance and on high‐threshold Ca 2+ spikes to initiate and boost the depolarizing phase of oscillations. The repolarization is initiated by TEA‐sensitive K + conductance and is controlled by the sAHP. These results suggest a role of interactions between NMDA conductance and intrinsic membrane properties in generating the CA1 θ‐rhythm. Hippocampus 2003;13:10067. © 2003 Wiley‐Liss, Inc.