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Focal photolysis of caged glutamate produces long-term depression of hippocampal glutamate receptors

Abstract

Separating contributions of pre- and postsynaptic factors to the maintenance of long-term potentiation (LTP) and long-term depression (LTD) has been confounded by their experimental interdependence. To isolate the postsynaptic contribution, glutamate-receptor-mediated currents were elicited by localized photolysis of caged glutamate in small spots along the dendrites of CA1 hippocampal pyramidal cells. With synaptic transmission blocked, pairing depolarization of pyramidal cells with repeated photolysis of caged glutamate at one site markedly and persistently depressed subsequent responses to glutamate; responses at a second, unpaired site were unchanged. Like synaptically induced LTD at the CA3–CA1 synapse, this depression was site specific, NMDA-receptor dependent and blocked by protein-phosphatase inhibitors. Thus, robust, persistent alterations of postsynaptic glutamate receptor efficacy can occur without presynaptic neurotransmitter release.

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Figure 1: Focal photolysis of caged glutamate elicits fast glutamatergic currents.
Figure 2: Pairing depolarization of pyramidal cells with focal glutamate photolysis induces site-specific, long-term depression.
Figure 3: Long-term depression of glutamate responses requires activation of NMDA receptors.
Figure 4: Long-term depression of glutamate responses requires protein phosphatases.

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Acknowledgements

We thank R. Givens for the gift of p-hydroxyphenacyl-glutamate. We are grateful to R. Timberlake and the physics shop at Duke University for support, M. Gray for histological work, and D. Nelson for writing the data acquisition and analysis programs. We also thank L. McMahon, F. Schweizer, and T. Tucker for discussions and comments on the manuscript. Supported by EY06730-02 to K.K. and NS30500-06A1 to J.A.K. L.C.K. is an investigator at the Howard Hughes Medical Institute.

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Correspondence to Karl Kandler.

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Kandler, K., Katz, L. & Kauer, J. Focal photolysis of caged glutamate produces long-term depression of hippocampal glutamate receptors. Nat Neurosci 1, 119–123 (1998). https://doi.org/10.1038/368

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