Biophysical and synaptic properties of NMDA receptors in the lateral habenula.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_6B842D4D467D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Biophysical and synaptic properties of NMDA receptors in the lateral habenula.
Journal
Neuropharmacology
Author(s)
Nuno-Perez A., Mondoloni S., Tchenio A., Lecca S., Mameli M.
ISSN
1873-7064 (Electronic)
ISSN-L
0028-3908
Publication state
Published
Issued date
15/09/2021
Peer-reviewed
Oui
Volume
196
Pages
108718
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Excitatory synaptic transmission in the lateral habenula (LHb), an evolutionarily ancient subcortical structure, encodes aversive stimuli and affective states. Habenular glutamatergic synapses contribute to these processes partly through the activation of AMPA receptors. Yet, N-methyl-d-aspartate receptors (NMDARs) are also expressed in the LHb and support the emergence of depressive symptoms. Indeed, local NMDAR blockade in the LHb rescues anhedonia and behavioral despair in rodent models of depression. However, the subunit composition and biophysical properties of habenular NMDARs remain unknown, thereby hindering their study in the context of mental health. Here, we performed electrophysiological recordings and optogenetic-assisted circuit mapping in mice, to study pharmacologically-isolated NMDAR currents in LHb neurons that receive innervation from different brain regions (entopeduncular nucleus, lateral hypothalamic area, bed nucleus of the stria terminalis, or ventral tegmental area). This systematic approach revealed that habenular NMDAR currents are sensitive to TCN and ifenprodil - drugs that specifically inhibit GluN2A- and GluN2B-containing NMDARs, respectively. Whilst these pharmacological effects were consistently observed across inputs, we detected region-specific differences in the current-voltage relationship and decay time of NMDAR currents. Finally, inspired by the firing of LHb neurons in vivo, we designed a burst protocol capable of eliciting calcium-dependent long-term potentiation of habenular NMDAR transmission ex vivo. Altogether, we define basic biophysical and synaptic properties of NMDARs in LHb neurons, opening new avenues for studying their plasticity processes in physiological as well as pathological contexts.
Keywords
Animals, Entopeduncular Nucleus, Excitatory Amino Acid Antagonists/pharmacology, Habenula/cytology, Habenula/drug effects, Habenula/metabolism, Habenula/physiology, Hypothalamic Area, Lateral, Long-Term Potentiation/physiology, Mice, Neural Pathways, Neurons/drug effects, Neurons/metabolism, Neurons/physiology, Optogenetics, Patch-Clamp Techniques, Piperidines/pharmacology, Receptors, N-Methyl-D-Aspartate/metabolism, Receptors, N-Methyl-D-Aspartate/physiology, Septal Nuclei, Sulfonamides/pharmacology, Synapses/drug effects, Synapses/metabolism, Synapses/physiology, Ventral Tegmental Area, Lateral habenula, Long-term potentiation, NMDA receptors, Subunit composition
Pubmed
Web of science
Open Access
Yes
Create date
26/07/2021 9:53
Last modification date
18/07/2024 7:13
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