Journal
NEUROPHARMACOLOGY
Volume 52, Issue 1, Pages 176-184Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2006.07.021
Keywords
long-term potentiation; long-term depression; nitric oxide; endocannabinoid; neocortical layer 5
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Funding
- Medical Research Council [G0700188] Funding Source: Medline
- NEI NIH HHS [EY 014439] Funding Source: Medline
- NIMH NIH HHS [MH 66338] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- NATIONAL EYE INSTITUTE [R01EY014439] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH066338] Funding Source: NIH RePORTER
- MRC [G0700188] Funding Source: UKRI
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Long-term potentiation and depression (LTP and LTD) are cellular plasticity phenomena expressed at a variety of central synapses, and are thought to contribute to learning and developmental changes in circuitry. Recurrent neocortical layer-5 synapses are thought to express a presynaptic form of LTP that influences the short-term plasticity of the synapse. Here we show that changes in synaptic strength elicited by pairing high frequency pre- and postsynaptic firing at this synapse result from a mixture of presynaptic and postsynaptic forms of plasticity, as assessed by the analysis of changes in coefficient of variation, short-term plasticity, and NMDA:AMPA current ratios. Pharmacological dissection of this plasticity revealed that block of presynaptic LTD with an endocannabinoid inhibitor enhanced LTP, while the apparently presynaptic component of UP could be prevented by induction in the presence of blockers of nitric oxide. These data suggest that correlated high-frequency firing at layer-5 synapses simultaneously induces a mixture of presynaptic LTD, presynaptic LTP, and postsynaptic LTP. (c) 2006 Elsevier Ltd. All rights reserved.
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