Dopamine D1 and glutamate receptors co-operate with brain-derived neurotrophic factor (BDNF) and TrkB to modulate ERK signaling in adult striatal slices

Morella, Ilaria ORCID: https://orcid.org/0000-0001-5691-5400, Hallum, Harriet and Brambilla, Riccardo ORCID: https://orcid.org/0000-0003-3569-5706 2020. Dopamine D1 and glutamate receptors co-operate with brain-derived neurotrophic factor (BDNF) and TrkB to modulate ERK signaling in adult striatal slices. Frontiers in Cellular Neuroscience 14 , 564106. 10.3389/fncel.2020.564106

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Abstract

In the striatum, the input nucleus of the basal ganglia, the extracellular-signal-regulated kinase (ERK) pathway, necessary for various forms of behavioral plasticity, is triggered by the combined engagement of dopamine D1 and ionotropic glutamate receptors. In this study, we investigated the potential crosstalk between glutamatergic, dopaminergic, and brain-derived neurotrophic factor (BDNF)-TrkB inputs to ERK cascade by using an ex vivo model of mouse striatal slices. Our results confirmed that the concomitant stimulation of D1 and glutamate receptors is necessary to activate ERK in striatal medium spiny neurons (MSNs). Moreover, we found that ERK activation is significantly enhanced when BDNF is co-applied either with glutamate or the D1 agonist SKF38393, supporting the idea of possible integration between BDNF, glutamate, and D1R-mediated signaling. Interestingly, ERK activation via BDNF-TrkB is upregulated upon blockade of either AMPAR/NMDAR or D1 receptors, suggesting a negative regulatory action of these two neurotransmitter systems on BDNF-mediated signaling. However, the observed enhancement of ERK1/2 phosphorylation does not result in corresponding downstream signaling changes at the nuclear level. Conversely, the TrkB antagonist cyclotraxin B partially prevents glutamate- and D1-mediated ERK activation. Altogether, these results suggest a complex and unexpected interaction among dopaminergic, glutamatergic, and BDNF receptor systems to modulate the ERK pathway in striatal neurons.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	is is an open-access articledistributed under the terms of the Creative Commons Attribution License (CC BY).The use, distribution or reproduction in other forums is permitted, provided theoriginal author(s) and the copyright owner(s) are credited and that the originalpublication in this journal is cited, in accordance with accepted academic practice.No use, distribution or reproduction is permitted which does not comply withthese terms.
Publisher:	Frontiers
ISSN:	1662-5102
Date of First Compliant Deposit:	3 December 2020
Date of Acceptance:	19 October 2020
Last Modified:	08 May 2023 07:10
URI:	https://orca.cardiff.ac.uk/id/eprint/136760

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