Activation Of Nmda Receptors In Hippocampal Area Ca1 By Low And High-frequency Orthodromic Stimulation And Their Contribution To Induction Of Long-term Potentiation
2-amino-5-phosphonovaleric acid; amino-acid receptors; cells; clamp; dentate gyrus; hippocampus; invitro rat hippocampus; kitten visual-cortex; n-methyl-d-aspartate receptor; Neurosciences & Neurology; pyramidal; responses; single-electrode voltage; slices; spinal-cord neurons; stimulation; synaptic plasticity; synaptic transmission; tetanic; time course
N-methyl-D-aspartate (NMDA) receptors are important in many instances of synaptic plasticity. In hippocampal area CA1, long-term potentiation (LTP) can be induced by both NMDA receptor-dependent and -independent mechanisms. Using intracellular recordings and single-electrode voltage clamp, we isolated and characterized NMDA receptor-mediated synaptic responses. NMDA receptor-mediated responses evoked by low frequency orthodromic stimulation were inhibited in a dose-dependent manner by the competitive antagonist D,L-2-amino-5-phosphonovaleric acid (APV). High frequency (tetanic) stimulation, which facilitates synaptic release of glutamate, failed to overcome the blockade of NMDA receptors by APV. Using extracellular recordings of field potentials, we studied the contribution of NMDA receptors to LTP induced by different patterns of tetanic stimulation. LTP was inhibited in a dose-dependent manner by APV, but was more sensitive to APV than were NMDA receptor-mediated synaptic responses. This most likely reflects a threshold for NMDA receptor activation in LTP induction. A component of LTP that resisted blockade by APV was induced by high (200 Hz), but not low (25 Hz), frequency tetanization. This NMDA receptor-independent component of LTP persisted for > 4 hours and accounted for approximately half the potentiation induced by 200 Hz tetanization. Procedures necessary to induce LTP at the Schaffer collateral/commissural synapses in area CA1 by both NMDA receptor-dependent and -independent mechanisms are now well characterized. Using the same neuronal population, it will be possible to ask if processes involved in the maintenance of LTP are shared even when LTP is induced through two different mechanisms. (C) 1994 Wiley-Liss, Inc.
Grover L M; Teyler T J
Synapse
1994
1994-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/syn.890160108" target="_blank" rel="noreferrer noopener">10.1002/syn.890160108</a>
Different Mechanisms May Be Required For Maintenance Of Nimda Receptor-dependent And Independent Forms Of Long-term Potentiation
activation; area; ca1; calcium; calcium channels; calmodulin inhibitors; d-aspartate receptors; dentate gyrus; depression; glutamate; hippocampal slice; induction; Neurosciences & Neurology; protein kinase; protein-kinase-c; rat hippocampal slices
In hippocampal area CA1, long-term potentiation (LTP) is induced by tetanic stimulation protocols that activate N-methyl-D-aspartate (NMDA) receptors. In addition, some stimulation protocols can induce LTP during NMDA receptor blockade. An initial signal in both NMDA receptor-dependent and independent LTPs is increased intracellular Ca2+ concentration in postsynaptic neurons. It therefore seems possible that subsequent steps leading to expression and maintenance of potentiation are shared whether or not LTP is induced through NMDA receptor activation. We tested this hypothesis by applying a broad spectrum protein kinase inhibitor, previously shown to inhibit NMDA receptor-dependent LTP. In agreement with earlier reports, we found that H-7 inhibited NMDA receptor-dependent LTP when applied either during tetanic stimulation, or beginning 30 min following tetanic stimulation. In contrast, NMDA receptor-independent LTP was not inhibited by H-7 applied during or following tetanic stimulation. We also tested for mutual occlusion between NMDA receptor-dependent and independent LTPs. Although induction of NMDA receptor-independent LTP did not occlude later induction of NMDA receptor-dependent LTP, induction of NMDA receptor-dependent LTP did occlude NMDA receptor-independent LTP. While the kinase inhibitor experiment showed a clear difference between NMDA receptor-dependent and independent LTPs, the occlusion experiments suggest an interaction between the signalling pathways for the two LTPs. (C) 1995 Wiley-Liss, Inc.
Grover L M; Teyler T J
Synapse
1995
1995-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/syn.890190208" target="_blank" rel="noreferrer noopener">10.1002/syn.890190208</a>