NMDA Receptor Antagonists Reveal Age-Dependent Differences in the Properties of Visual Cortical Plasticity
| Autor: | Lindsey R. Wilfley, Vera Valakh, Benjamin D. Philpot, Paul G. Middlebrooks, Koji Yashiro, Jacqueline de Marchena, Adam C. Roberts |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Aging Patch-Clamp Techniques Physiology Protein subunit Blotting Western Long-Term Potentiation Age dependent In Vitro Techniques Biology Plasticity Receptors N-Methyl-D-Aspartate Mice Piperidines Quinoxalines Metaplasticity Neuroplasticity Animals Long-term depression Depression (differential diagnoses) Visual Cortex Mice Knockout Neuronal Plasticity musculoskeletal neural and ocular physiology General Neuroscience Articles Electrophysiology Mice Inbred C57BL nervous system Evoked Potentials Visual NMDA receptor Female Extracellular Space Excitatory Amino Acid Antagonists Neuroscience Subcellular Fractions |
| Zdroj: | Journal of Neurophysiology. 100:1936-1948 |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.90290.2008 |
| Popis: | The suggestion that NMDA receptor (NMDAR)-dependent plasticity is subunit specific, with NR2B-types required for long-term depression (LTD) and NR2A-types critical for the induction of long-term potentiation (LTP), has generated much attention and considerable debate. By investigating the suggested subunit-specific roles of NMDARs in the mouse primary visual cortex over development, we report several important findings that clarify the roles of NMDAR subtypes in synaptic plasticity. We observed that LTD was not attenuated by application of ifenprodil, an NR2B-type antagonist, or NVP-AAM007, a less selective NR2A-type antagonist. However, we were surprised that NVP-AAM007 completely blocked adult LTP (postnatal day (P) 45–90), while only modestly affecting juvenile LTP (P21-28). To assess whether this developmental transition reflected an increasing role for NR2A-type receptors with maturity, we characterized the specificity of NVP-AAM007. We found not only that NVP-AAM007 lacks discernable subunit specificity but also that the effects of NVP-AAM077 on LTP could be mimicked using subsaturating concentrations of APV, a global NMDAR antagonist. These results indicate that the effects of NVP-AAM077 on synaptic plasticity are largely explained by nonspecific blockade of NMDARs. Moreover our findings are the first to reveal a developmental increase in the sensitivity of LTP to NMDAR antagonism. We suggest that discrepant reports describing the effect of NVP-AAM077 on LTP may be partially explained by this developmental shift in the properties of LTP. These results indicate that the degree of NMDAR activation required for LTP increases with development, providing insight into a novel underlying mechanism governing the properties of synaptic plasticity. |
| Databáze: | OpenAIRE |
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