Differential calcium-dependent modulation of NMDA currents in CA1 and CA3 hippocampal pyramidal cells

TY - JOUR

T1 - Differential calcium-dependent modulation of NMDA currents in CA1 and CA3 hippocampal pyramidal cells

AU - Grishin, Anton A

AU - Gee, Christine E

AU - Gerber, Urs

AU - Benquet, Pascal

PY - 2004/1/14

Y1 - 2004/1/14

N2 - Neuronal Ca2+ influx via NMDA receptors (NMDARs) is essential for the development and plasticity of synapses but also triggers excitotoxic cell death when critical intracellular levels are exceeded. Therefore, finely equilibrated mechanisms are necessary to ensure that NMDAR function is maintained within a homeostatic range. Here we describe a pronounced difference in the modulation of NMDA currents in two closely related hippocampal cell types, the CA1 and the CA3 pyramidal cells (PCs). Manipulations that increase intracellular Ca2+ levels strongly depressed NMDA currents in CA3 with only minor effects in CA1 PCs. Furthermore, activation of G(q)-coupled metabotropic receptors potentiated NMDA currents in CA1 PCs but depressed them in CA3 PCs. Interestingly, the CA3 type modulation of NMDARs could be converted into CA1-like behavior, and vice versa, by increasing Ca2+ buffering in CA3 cells or decreasing Ca2+ buffering in CA1 cells, respectively. Our data suggest that a differential Ca2+ sensitivity of the regulatory cascades targeting NMDARs plays a key role in determining the direction and magnitude of NMDA responses in various types of neurons. These findings may have important implications for NMDA receptor-dependent synaptic plasticity and the differential sensitivity of CA1 and CA3 PCs to NMDAR-dependent ischemic cell death.

AB - Neuronal Ca2+ influx via NMDA receptors (NMDARs) is essential for the development and plasticity of synapses but also triggers excitotoxic cell death when critical intracellular levels are exceeded. Therefore, finely equilibrated mechanisms are necessary to ensure that NMDAR function is maintained within a homeostatic range. Here we describe a pronounced difference in the modulation of NMDA currents in two closely related hippocampal cell types, the CA1 and the CA3 pyramidal cells (PCs). Manipulations that increase intracellular Ca2+ levels strongly depressed NMDA currents in CA3 with only minor effects in CA1 PCs. Furthermore, activation of G(q)-coupled metabotropic receptors potentiated NMDA currents in CA1 PCs but depressed them in CA3 PCs. Interestingly, the CA3 type modulation of NMDARs could be converted into CA1-like behavior, and vice versa, by increasing Ca2+ buffering in CA3 cells or decreasing Ca2+ buffering in CA1 cells, respectively. Our data suggest that a differential Ca2+ sensitivity of the regulatory cascades targeting NMDARs plays a key role in determining the direction and magnitude of NMDA responses in various types of neurons. These findings may have important implications for NMDA receptor-dependent synaptic plasticity and the differential sensitivity of CA1 and CA3 PCs to NMDAR-dependent ischemic cell death.

KW - Animals

KW - Calcium

KW - Cells, Cultured

KW - Electric Conductivity

KW - Hippocampus

KW - Neuronal Plasticity

KW - Pyramidal Cells

KW - Rats

KW - Rats, Wistar

KW - Receptors, Metabotropic Glutamate

KW - Receptors, N-Methyl-D-Aspartate

KW - Signal Transduction

U2 - 10.1523/JNEUROSCI.4933-03.2004

DO - 10.1523/JNEUROSCI.4933-03.2004

M3 - SCORING: Journal article

C2 - 14724233

VL - 24

SP - 350

EP - 355

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 2

ER -