Focal photolysis of caged glutamate produces long-term depression of hippocampal glutamate receptors.
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.
Kandler
K
K
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. kkarl+@pitt.edu
Katz
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LC
Kauer
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D000818:Animals; D003712:Dendrites / Q000378:metabolism; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005971:Glutamates / Q000528:radiation effects*; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010782:Photolysis; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology
C102508:(carboxy-2-nitrobenzyl)glutamic acid; D004791:Enzyme Inhibitors; D005971:Glutamates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D010749:Phosphoprotein Phosphatases