Journal Article

LTP requires a reserve pool of glutamate receptors independent of subunit type

Shi, Yun, Lu, Wei, Cerpas, Manuel, Nicoll, Roger A., Granger, Adam J.

2013

Overview

Long-term potentiation (LTP) of synaptic transmission is thought to be an important cellular mechanism underlying memory formation. A widely accepted model posits that LTP requires the cytoplasmic carboxyl tail (C-tail) of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GluA1. To find the minimum necessary requirement of the GluA1 C-tail for LTP in mouse CA1 hippocampal pyramidal neurons, we used a single-cell molecular replacement strategy to replace all endogenous AMPA receptors with transfected subunits. In contrast to the prevailing model, we found no requirement of the GluA1 C-tail for LTP. In fact, replacement with the GluA2 subunit showed normal LTP, as did an artificially expressed kainate receptor not normally found at these synapses. The only conditions under which LTP was impaired were those with markedly decreased AMPA receptor surface expression, indicating a requirement for a reserve pool of receptors. These results demonstrate the synapse’s remarkable flexibility to potentiate with a variety of glutamate receptor subtypes, requiring a fundamental change in our thinking with regard to the core molecular events underlying synaptic plasticity. The minimal possible requirement for AMPA receptor trafficking during long-term potentiation is explored, revealing that no region of the receptor subunit is necessary, in contrast with previous work; the only requirement for LTP seems to be a large reserve of glutamate receptors. A rethink on LTP and memory Learning and memory formation are thought to involve long-term potentiation (LTP), a rapid and lasting increase in synaptic strength between two neurons. LTP has been well described at glutamatergic synapses in the hippocampus, a region of the brain that is required for the formation of new memories. This study suggests, however, that the prevailing model for LTP, focusing on a single neurotransmitter receptor protein — the AMPA receptor subunit GluA1 — needs to be reconsidered. Rather, it seems that no one particular glutamate receptor is critically important for the production of LTP: if there is a large enough pool available locally for a synapse, LTP will occur.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/2591/2592 / 631/378/548 / Animals / Binding sites / Brain research / Experiments / Gene Deletion / Glutamate / Humanities and Social Sciences / Long-term potentiation / Long-Term Potentiation - physiology / Mice / Models, Neurological / multidisciplinary / Neural receptors / Neural transmission / Neurons / Phosphorylation / Physiological aspects / Protein folding / Protein Structure, Tertiary / Protein Subunits - metabolism / Protein Transport / Receptors, AMPA - chemistry / Receptors, AMPA - deficiency / Receptors, AMPA - genetics / Receptors, AMPA - metabolism / Receptors, Ionotropic Glutamate - chemistry / Receptors, Ionotropic Glutamate - metabolism / Receptors, Kainic Acid - metabolism / Science / Synapses - metabolism / Synaptic Transmission