Group III metabotropic glutamate receptors gate long-term potentiation and synaptic tagging/capture in rat hippocampal area CA2.

Ananya Dasgupta,Thomas Behnisch,Amrita Benoy,Ka Lam Karen Pang,Yu Jia Lim,Nimmi Baby,Krishna Kumar,Sreedharan Sajikumar

doi:10.7554/elife.55344

Ananya Dasgupta, Thomas Behnisch + Show 6 more

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https://doi.org/10.7554/elife.55344

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Journal: eLife	Publication Date: Apr 20, 2020
Citations: 27	License type: CC BY 4.0

Affiliation: Fudan University, National University of Singapore

Abstract

Metabotropic glutamate receptors (mGluRs) play an important role in synaptic plasticity and memory and are largely classified based on amino acid sequence homology and pharmacological properties. Among group III metabotropic glutamate receptors, mGluR7 and mGluR4 show high relative expression in the rat hippocampal area CA2. Group III metabotropic glutamate receptors are known to down-regulate cAMP-dependent signaling pathways via the activation of Gi/o proteins. Here, we provide evidence that inhibition of group III mGluRs by specific antagonists permits an NMDA receptor- and protein synthesis-dependent long-lasting synaptic potentiation in the apparently long-term potentiation (LTP)-resistant Schaffer collateral (SC)-CA2 synapses. Moreover, long-lasting potentiation of these synapses transforms a transient synaptic potentiation of the entorhinal cortical (EC)-CA2 synapses into a stable long-lasting LTP, in accordance with the synaptic tagging/capture hypothesis (STC). Furthermore, this study also sheds light on the role of ERK/MAPK protein signaling and the downregulation of STEP protein in the group III mGluR inhibition-mediated plasticity in the hippocampal CA2 region, identifying them as critical molecular players. Thus, the regulation of group III mGluRs provides a conducive environment for the SC-CA2 synapses to respond to events that could lead to activity-dependent synaptic plasticity.

Highlights

Synaptic plasticity and memory formation have remained fascinating areas of neuroscience research and have been widely studied in the hippocampus, a brain area that is primarily responsible for memory formation and spatial navigation
Schaffer collateral-CA2 synapses are known from previous studies to be resistant to activity-dependent long-term potentiation (LTP) induced by conventional induction protocols that are effective in CA1 neurons (Zhao et al, 2007)
We know that hippocampal CA2 plays a crucial role in social memory formation (Hitti and Siegelbaum, 2014; Tzakis and Holahan, 2019), we still do not fully understand how the CA2 region’s unique molecular and cellular properties contribute to its function at the circuit and Neuroscience behavioural level

Summary

Introduction

Synaptic plasticity and memory formation have remained fascinating areas of neuroscience research and have been widely studied in the hippocampus, a brain area that is primarily responsible for memory formation and spatial navigation. The hippocampal area CA2 has recently been the subject of much attention owing to its involvement in social memory formation and socio-cognitive information processing (Hitti and Siegelbaum, 2014; Pagani et al, 2015; Smith et al, 2016). The excitatory neurons in the CA2 area have unique intrinsic properties such as more negative resting membrane potentials (Zhao et al, 2007). Distal CA2 neurons receive strong excitatory inputs from layer II of the entorhinal cortex (EC-LII) directly and these EC-CA2 synapses express activity-dependent long-term potentiation (LTP) (Chevaleyre and Siegelbaum, 2010). The Schaffer collateral inputs (SC) from CA3 to CA2 do not support activity-dependent LTP in response to typical induction protocols (Zhao et al, 2007).

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