To study the link between LTP, synaptic strengthening and learning the authors used a single-whisker experience (SWE) protocol in which all but one of a mouse's whiskers were removed, resulting in the potentiation of synapses within the barrel cortical column that receives input from the remaining whisker. They demonstrated that administering an NMDAR antagonist during the initial phase of SWE prevented this synaptic strengthening. In addition, application of an NMDAR antagonist blocked the LTP that was induced by pairing (a procedure in which presynaptic stimulation is paired with postsynaptic depolarization) in barrel column synapses of control mice, indicating that NMDAR activation is required for both in vivo SWE-induced synaptic strengthening and in vitro LTP in barrel cortex synapses.
Interestingly, after 24 hours of SWE, pairing could no longer potentiate barrel column synapses — in other words, prolonged SWE caused the occlusion of further LTP at these synapses. In the past, this has been interpreted as evidence that SWE induced LTP early on and that no further LTP could be elicited as SWE continued. Crucially, however, Clem et al. showed that application of an NMDAR antagonist prevented this SWE-induced occlusion of LTP, indicating that NMDAR activation acts to suppress synaptic strengthening after prolonged sensory stimulation. Application of an mGluR antagonist plus an NMDAR antagonist to barrel column slices from SWE mice completely prevented pairing-induced LTP, suggesting that mGluR counteracts the NMDAR-mediated synaptic depression and maintains synaptic plasticity after long-term sensory experience.
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