Cellular mechanisms underlying the rhythmic bursts induced by NMDA microiontophoresis at the apical dendrites of CA1 pyramidal neurons

Bonansco, C; Buno, W


This article reports the cellular mechanisms underlying a form of intracellular "theta-like" (theta-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 (approximate to6 Hz; approximate to20 mV; approximate to2-5 APs) were evoked in all cells. The response lasted approximate to2 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 muM), of non NMDA receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (20 muM) and of synaptic inhibition by bicuculline (50 ILM) and picrotoxin (50 muM) did not prevent NMDA oscillation. Inhibition of the voltage dependence of the NMDA conductance in Mg2+-free Ringer's solution blocked oscillations. Preventing Ca2+ influx with Ca2+-free and Co2+ (2-mM) solutions and block of the slow Ca2+-dependent afterhyperpolarization (sAHP) by carbamilcholine (5 muM), isoproterenol (10 muM), and intracellular BAPTA blocked NMDA oscillations. Inhibition of L-type Ca 2+ conductance with nifedipine (30 muM) 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, theta-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 theta-rhythm. Hippocampus 2003;13:150-163. (C) 2003 Wiley-Liss, Inc.

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Título según WOS: ID WOS:000181005800013 Not found in local WOS DB
Título de la Revista: HIPPOCAMPUS
Volumen: 13
Número: 1
Editorial: Wiley
Fecha de publicación: 2003
Página de inicio: 150
Página final: 163


Notas: ISI