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

• Published in: Hippocampus Vol. 13; no. 1; pp. 150 - 163
• Main Authors: Bonansco, Christian, Buño, Washington
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 2003
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Calcium Channel Blockers - pharmacology; Calcium Signaling - drug effects; Calcium Signaling - physiology; Dendrites - drug effects; Dendrites - metabolism; Dendritic Ca2+ spikes; Excitatory Amino Acid Antagonists - pharmacology; GABA Antagonists - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; In vitro oscillations; Iontophoresis; N-Methylaspartate - pharmacology; NMDA bursts; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels - metabolism; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Slow afterhyperpolarization; Sodium Channel Blockers - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Theta rhythm; Theta Rhythm - drug effects
• ISSN: 1050-9631; 1098-1063
• DOI: 10.1002/hipo.10067

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 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 μM), isoproterenol (10 μM), and intracellular BAPTA blocked NMDA oscillations. Inhibition of L‐type Ca2+ 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 Ca2+ 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.