title: Presynaptic induction and expression of timing-dependent long-term depression demonstrated by compartment-specific photorelease of a use-dependent NMDA receptor antagonist.
abstract: NMDA receptors are important for synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). To help investigate the precise location of the NMDA receptors that are required for different types of synaptic plasticity, we synthesized a caged form of the use-dependent NMDA receptor antagonist MK801, which we loaded into individual neurons in vitro, followed by compartment-specific uncaging. We used this method to investigate timing-dependent plasticity at layer 4-layer 2/3 synapses of mouse barrel cortex. Somatodendritic photorelease of MK801 in the postsynaptic neuron produced a use-dependent block of synaptic NMDA receptor-mediated currents and prevented the induction of LTP. Compartment-specific photorelease of MK801 in the presynaptic neuron showed that axonal, but not somatodendritic, presynaptic NMDA receptors are required for induction of LTD. The rate of use-dependent block of postsynaptic NMDA receptor current was slower following induction of LTD, consistent with a presynaptic locus of expression. Thus, this new caged compound has demonstrated the axonal location of NMDA receptors required for induction and the presynaptic locus of expression of LTD at layer 4-layer 2/3 synapses.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, U.K.|Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, U.K.|Department of Physiology, Anatomy and Cellular Biology, University Pablo de Olavide, Ctra. de Utrera, Km. 1, 41013 Seville, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Moreno
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, U.K.|Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, U.K.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kohl
authors.affiliation: Department of Chemistry, University of Oxford, Oxford OX1 3TA, U.K.
authors.forename: James E
authors.initials: JE
authors.lastname: Reeve
authors.affiliation: Department of Chemistry, University of Oxford, Oxford OX1 3TA, U.K.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Eaton
authors.affiliation: Department of Chemistry, University of Oxford, Oxford OX1 3TA, U.K.
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Collins
authors.affiliation: Department of Chemistry, University of Oxford, Oxford OX1 3TA, U.K.
authors.forename: Harry L
authors.initials: HL
authors.lastname: Anderson
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, U.K.|Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, U.K.
authors.forename: Ole
authors.initials: O
authors.lastname: Paulsen
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate