On the Role of Calcium-Permeable AMPARs in Long-Term Potentiation and Synaptic Tagging in the Rodent Hippocampus.

Pojeong Park,John Georgiou,Graham L. Collingridge,Thomas M. Sanderson,Min Zhuo,Heather Kang,Bong-Kiun Kaang,Zuner A. Bortolotto

doi:10.3389/fnsyn.2019.00004

Abstract

Classically, long-term potentiation (LTP) at hippocampal CA1 synapses is triggered by the synaptic activation of NMDA receptors (NMDARs). More recently, it has been shown that calcium-permeable (CP)-AMPARs can also trigger synaptic plasticity at these synapses. Specifically, their activation is required for the PKA and protein synthesis dependent component of LTP that is typically induced by delivery of spaced trains of high frequency stimulation. Here we present new data that build upon these ideas, including the requirement for low frequency synaptic activation and NMDAR dependence. We also show that a spaced theta burst stimulation (sTBS) protocol induces a heterosynaptic potentiation of baseline responses via activation of CP-AMPARs. Finally, we present data that implicate CP-AMPARs in synaptic tagging and capture, a fundamental process that is associated with the protein synthesis-dependent component of LTP. We have studied how a sTBS can augment the level of LTP generated by a weak TBS (wTBS), delivered 30 min later to an independent input. We show that inhibition of CP-AMPARs during the sTBS eliminates, and that inhibition of CP-AMPARs during the wTBS reduces, this facilitation of LTP. These data suggest that CP-AMPARs are crucial for the protein synthesis-dependent component of LTP and its heterosynaptic nature.

Highlights

Long-term potentiation (LTP) has been most extensively studied at the excitatory synapses made between CA3 and CA1 pyramidal neurons
Since we have found that CPAMPARs are required for LTP2 (Park et al, 2016) we wondered if these receptors are necessary to initiate the protein synthesis machinery that generates these hypothetical plasticity related proteins (PRPs)
We have found that the activation of CPAMPARs during a spaced theta burst stimulus (TBS) that initiates LTP2 locally, is required to facilitate LTP on an independent input induced by a weak TBS

Summary

Introduction

Long-term potentiation (LTP) has been most extensively studied at the excitatory synapses made between CA3 and CA1 pyramidal neurons (see Bliss et al, 2018 for a recent review) At these synapses three distinct forms of NMDAR-dependent, transcriptionally independent forms of synaptic potentiation have been identified that overlap in time; short-term potentiation (STP), LTP1 and LTP2. The latter form of synaptic plasticity is defined by its dependence on the activation of PKA and protein synthesis (Frey et al, 1993; Matthies and Reymann, 1993; Frey and Morris, 1998; Reymann and Frey, 2007; Bliss et al, 2018).

Results

Discussion

Conclusion