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Presynaptic Induction and Expression of Timing-Dependent Long-Term Depression Demonstrated by Compartment-Specific Photorelease of a Use-Dependent NMDA Receptor Antagonist

Presynaptic Induction and Expression of Timing-Dependent Long-Term Depression Demonstrated by Compartment-Specific Photorelease of a Use-Dependent NMDA Receptor Antagonist

Antonio Rodríguez-Moreno, Michael M Kohl, James E Reeve, Thomas R Eaton, Hazel A Collins, Harry L Anderson, Ole Paulsen

J Neurosci. 2011 Jun 8;31(23):8564-8569.

PMID: 21653860

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP217176915	Caged MK801		217176-91-5	Price

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