Abstract
We tested the proposal that the C-terminal domain (CTD) of the AMPAR subunit GluA1 is required for LTP. We found that a knock-in mouse lacking the CTD of GluA1 expresses normal LTP and spatial memory, assayed by the Morris water maze. Our results support a model in which LTP generates synaptic slots, which capture passively diffusing AMPARs.
Highlights
Long-term potentiation (LTP) requires the activity-dependent trafficking of AMPA receptors (AMPARs) to the synapse (Collingridge et al, 2004; Malinow and Malenka, 2002; Nicoll, 2017)
We previously showed that replacement of endogenous GluA2 subunits with GluA1/A2CTD resulted in functional AMPARs, which supported homeostatic synaptic scaling (Ancona Esselmann et al, 2017)
We replaced all endogenous AMPARs with heteromeric GluA1/A2CTD-GluA2 receptors in hippocampal CA1 pyramidal neurons
Summary
Long-term potentiation (LTP) requires the activity-dependent trafficking of AMPA receptors (AMPARs) to the synapse (Collingridge et al, 2004; Malinow and Malenka, 2002; Nicoll, 2017). The prevailing, receptor centric, LTP model, posits that LTP-mediated covalent modification of the intracellular carboxyterminal domain (CTD, referred to as C-tail) of GluA1 results in the capture of these modified GluA1 containing receptors by preexisting ‘slots’ in the postsynaptic density (PSD) (Hayashi et al, 2000; Huganir and Nicoll, 2013; Malinow and Malenka, 2002; Shi et al, 2001), either by increasing the surface pool of AMPARs or the docking of AMPAR at the PSD The nature of these slots is unclear, but it is thought to involve binding sites on postsynaptic scaffolding proteins, such as PSD95. We concluded that AMPAR lacking the GluA1 subunit CTD can traffic normally to
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