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Monday, February 12th, 2018
Table of Contents

1 Introduction
5 PMID
 [F] Diseases Research  / PubMed Research Articles  /
Neuregulin 1/ErbB signalling modulates hippocampal mGluRI-dependent LTD and object recognition memory.

PubMed

 

Resource

Pharmacological research Feb ; ()

Authors

Ledonne A1; Mango D2; Latagliata EC3; Chiacchierini G4; Nobili A5; Nisticò R6; D'Amelio M7; Puglisi-Allegra S8; Mercuri NB9;

Author Information
  • 1Department of Experimental Neuroscience, Santa Lucia Foundation, Rome, Italy. Electronic address: adaledonne@gmail.com.
  • 2Pharmacology of Synaptic Disease Lab, European Brain Research Institute, Rome, Italy.
  • 3Department of Experimental Neuroscience, Santa Lucia Foundation, Rome, Italy.
  • 4Department of Psychology and "Daniel Bovet" Center, University "La Sapienza", Rome, Italy.
  • 5Department of Experimental Neuroscience, Santa Lucia Foundation, Rome, Italy; Department of Medicine, University Campus-Biomedico, Rome, Italy.
  • 6Pharmacology of Synaptic Disease Lab, European Brain Research Institute, Rome, Italy; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • 7Department of Experimental Neuroscience, Santa Lucia Foundation, Rome, Italy; Department of Medicine, University Campus-Biomedico, Rome, Italy.
  • 8Department of Experimental Neuroscience, Santa Lucia Foundation, Rome, Italy; Department of Psychology and "Daniel Bovet" Center, University "La Sapienza", Rome, Italy.
  • 9Department of Experimental Neuroscience, Santa Lucia Foundation, Rome, Italy; Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.

Abstract

The neurotrophic factors neuregulins (NRGs) and their receptors, ErbB tyrosine kinases, regulate neurotransmission, synaptic plasticity and cognitive functions and their alterations have been associated to different neuropsychiatric disorders. Group 1 metabotropic glutamate receptors (mGluRI)-dependent mechanisms are also altered in animal models of neuropsychiatric diseases, especially mGluRI-induced glutamatergic long-term depression (mGluRI-LTD), a form of synaptic plasticity critically involved in learning and memory. Despite this evidence, a potential link between NRGs/ErbB signalling and mGluRI-LTD has never been considered. Here, we aimed to test the hypothesis that NRGs/ErbB signalling regulates mGluRI functions in the hippocampus, thus controlling CA1 pyramidal neurons excitability and synaptic plasticity as well as mGluRI-dependent behaviors. We investigated the functional interaction between NRG1/ErbB signalling and mGluRI in hippocampal CA1 pyramidal neurons, by analyzing the effect of a pharmacological modulation of NRG1/ErbB signalling on the excitation of pyramidal neurons and on the LTD at CA3-CA1 synapses induced by an mGluRI agonist. Furthermore, we verified the involvement of ErbB signalling in mGluRI-dependent learning processes, by evaluating the consequence of an intrahippocampal in vivo injection of a pan-ErbB inhibitor in the object recognition test in mice, a learning task dependent on hippocampal mGluRI. We found that NRG1 potentiates mGluRI-dependent functions on pyramidal neurons excitability and synaptic plasticity at CA3-CA1 synapses. Further, endogenous ErbB signalling per se regulates, through mGluRI, neuronal excitability and LTD in CA1 pyramidal neurons, since ErbB inhibition reduces mGluRI-induced neuronal excitation and mGluRI-LTD. In vivo intrahippocampal injection of the ErbB inhibitor, PD158780, impairs mGluRI-LTD at CA3-CA1 synapses and affects the exploratory behavior in the object recognition test. Thus, our results identify a key role for NRG1/ErbB signalling in the regulation of hippocampal mGluRI-dependent synaptic and cognitive functions, whose alteration might contribute to the pathogenesis of different brain diseases.

Copyright © 2018 Elsevier Ltd. All rights reserved.

PMID

29427771

Others

Publication Type: Journal Article


This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.


Last Modified:   2016-03-27


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