Abstract
Long-term depression (LTD) is a form of synaptic plasticity that plays a major role in the activity-dependent reshaping of synaptic transmission. LTD is expressed as a decrease in synaptic AMPA receptor number, though the exact mechanism remains controversial. Several lines of evidence have suggested necessary roles for both the GluA1 and GluA2 subunits, and specifically certain interactions with their cytoplasmic tails. However, it is unclear if either GluA1 or GluA2 are absolutely required for LTD. We tested this hypothesis using constitutive knock-outs and single-cell molecular replacement of AMPA receptor subunits in mouse hippocampus. We found that neither GluA1 or GluA2 are required for normal expression of LTD, and indeed a normal decrease in synaptic transmission was observed in cells in which all endogenous AMPA receptors have been replaced by kainate receptors. Thus, LTD does not require removal of specific AMPA receptor subunits, but likely involves a more general modification of the synapse and its ability to anchor a broad range of receptor proteins.
Highlights
Excitatory synapses in the brain can modify their efficacy to store information in response to specific patterns of activity, either by strengthening through long-term potentiation (LTP) or weakening through long-term depression (LTD; Malenka and Bear, 2004)
To test whether GluA1 or GluA2 are required for LTD, we first used constitutive deletions of GluA1 and GluA2, respectively, which constitute the majority of synaptic AMPARs in CA1 pyramidal neurons (Wenthold et al, 1996; Lu et al, 2009)
In agreement with previous findings (Selcher et al, 2012), LTD expression was intact in GluA1 knockout slices, indistinguishable from LTD recorded from control slices (Figure 1A)
Summary
Excitatory synapses in the brain can modify their efficacy to store information in response to specific patterns of activity, either by strengthening through long-term potentiation (LTP) or weakening through long-term depression (LTD; Malenka and Bear, 2004). Both LTP and LTD are expressed through the insertion or removal, respectively, of AMPA-type glutamate receptors, which are heterotetramers comprised of different subunit proteins, GluA1-4 (Kessels and Malinow, 2009). GluA1 has been implicated in LTD expression by the finding that the GluA1 S845A knock-in mouse does not express LTD (Lee et al, 2003, 2010), though a recent study found that LTD expression is normal in GluA1 knockout mice (Selcher et al, 2012)
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