Activation of group I mGluRs is required for heterosynaptic priming of long-term potentiation in mouse hippocampus

Abstract

Metaplasticity involves changes in the state of neurons or synapses that influence their ability to generate synaptic plasticity. One form of heterosynaptic metaplasticity, known as synaptic tagging and capture (STC), has been intensively studied but the underlying mechanisms are not fully understood. In experiments using hippocampal slices prepared from C57BL/6J mice, we have examined the role of group I metabotropic glutamate receptors (mGluRs) in STC. We used a version of STC where a strong theta-burst stimulus (TBS), delivered to one set of Schaffer collateral-commissural pathway inputs to CA1, preceded a weak TBS delivered to a second independent set of inputs. We observed that, firstly, dual inhibition of mGluR1 and mGluR5, using YM 298198 and MTEP respectively, did not affect a form of protein synthesis-independent LTP (LTP1), but substantially inhibited a form of protein synthesis-dependent LTP (LTP2). Secondly, these inhibitors prevented the small heterosynaptic potentiation, which is often associated with LTP2. Thirdly, STC was abolished when these antagonists were applied either during the strong (priming) TBS or during the subsequent weak TBS at the independent pathway. It is proposed that the activation of group I mGluRs serves as a trigger for local protein synthesis both during the strong and weak TBS and, as such, are an integral part of the STC process. STC is involved in associative learning and memory, a cognitive function that is disrupted in many brain disorders including Alzheimers disease.