Cargando…

Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning

BACKGROUND: Reward-related learning, where animals form associations between rewards and stimuli (i.e., conditioned stimuli [CS]) that predict or accompany those rewards, is an essential adaptive function for survival. METHODS: In this study, we investigated the mechanisms underlying the acquisition...

Descripción completa

Detalles Bibliográficos
Autores principales: Galaj, Ewa, Barrera, Eddy D, Lynch, Olivia L, Diodati, Rachel, Thomas, Ashley, Schneider, Piper, Lenhard, Hayley, Vashisht, Apoorva, Ranaldi, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850662/
https://www.ncbi.nlm.nih.gov/pubmed/36402549
http://dx.doi.org/10.1093/ijnp/pyac076
_version_ 1784872230840172544
author Galaj, Ewa
Barrera, Eddy D
Lynch, Olivia L
Diodati, Rachel
Thomas, Ashley
Schneider, Piper
Lenhard, Hayley
Vashisht, Apoorva
Ranaldi, Robert
author_facet Galaj, Ewa
Barrera, Eddy D
Lynch, Olivia L
Diodati, Rachel
Thomas, Ashley
Schneider, Piper
Lenhard, Hayley
Vashisht, Apoorva
Ranaldi, Robert
author_sort Galaj, Ewa
collection PubMed
description BACKGROUND: Reward-related learning, where animals form associations between rewards and stimuli (i.e., conditioned stimuli [CS]) that predict or accompany those rewards, is an essential adaptive function for survival. METHODS: In this study, we investigated the mechanisms underlying the acquisition and performance of conditioned approach learning with a focus on the role of muscarinic acetylcholine (mACh) and NMDA glutamate receptors in the substantia nigra (SN), a brain region implicated in reward and motor processes. RESULTS: Using RNAscope in situ hybridization assays, we found that dopamine neurons of the SN express muscarinic (mACh5), NMDA2a, NMDA2b, and NMDA2d receptor mRNA but not mACh4. NMDA, but not mACh5, receptor mRNA was also found on SN GABA neurons. In a conditioned approach paradigm, rats were exposed to 3 or 7 conditioning sessions during which light/tone (CS) presentations were paired with delivery of food pellets, followed by a test session with CS-only presentations. Intra-SN microinjections of scopolamine (a mACh receptor antagonist) or AP-5 (a NMDA receptor antagonist) were made either prior to each conditioning session (to test their effects on acquisition) or prior to the CS-only test (to test their effects on expression of the learned response). Scopolamine and AP-5 produced dose-dependent significant reductions in the acquisition, but not performance, of conditioned approach. CONCLUSIONS: These results suggest that SN mACh and NMDA receptors are key players in the acquisition, but not the expression, of reward-related learning. Importantly, these findings redefine the role of the SN, which has traditionally been known for its involvement in motor processes, and suggest that the SN possesses attributes consistent with a function as a hub of integration of primary reward and CS signals.
format Online
Article
Text
id pubmed-9850662
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-98506622023-01-20 Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning Galaj, Ewa Barrera, Eddy D Lynch, Olivia L Diodati, Rachel Thomas, Ashley Schneider, Piper Lenhard, Hayley Vashisht, Apoorva Ranaldi, Robert Int J Neuropsychopharmacol Regular Research Article BACKGROUND: Reward-related learning, where animals form associations between rewards and stimuli (i.e., conditioned stimuli [CS]) that predict or accompany those rewards, is an essential adaptive function for survival. METHODS: In this study, we investigated the mechanisms underlying the acquisition and performance of conditioned approach learning with a focus on the role of muscarinic acetylcholine (mACh) and NMDA glutamate receptors in the substantia nigra (SN), a brain region implicated in reward and motor processes. RESULTS: Using RNAscope in situ hybridization assays, we found that dopamine neurons of the SN express muscarinic (mACh5), NMDA2a, NMDA2b, and NMDA2d receptor mRNA but not mACh4. NMDA, but not mACh5, receptor mRNA was also found on SN GABA neurons. In a conditioned approach paradigm, rats were exposed to 3 or 7 conditioning sessions during which light/tone (CS) presentations were paired with delivery of food pellets, followed by a test session with CS-only presentations. Intra-SN microinjections of scopolamine (a mACh receptor antagonist) or AP-5 (a NMDA receptor antagonist) were made either prior to each conditioning session (to test their effects on acquisition) or prior to the CS-only test (to test their effects on expression of the learned response). Scopolamine and AP-5 produced dose-dependent significant reductions in the acquisition, but not performance, of conditioned approach. CONCLUSIONS: These results suggest that SN mACh and NMDA receptors are key players in the acquisition, but not the expression, of reward-related learning. Importantly, these findings redefine the role of the SN, which has traditionally been known for its involvement in motor processes, and suggest that the SN possesses attributes consistent with a function as a hub of integration of primary reward and CS signals. Oxford University Press 2022-11-19 /pmc/articles/PMC9850662/ /pubmed/36402549 http://dx.doi.org/10.1093/ijnp/pyac076 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of CINP. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Research Article
Galaj, Ewa
Barrera, Eddy D
Lynch, Olivia L
Diodati, Rachel
Thomas, Ashley
Schneider, Piper
Lenhard, Hayley
Vashisht, Apoorva
Ranaldi, Robert
Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning
title Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning
title_full Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning
title_fullStr Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning
title_full_unstemmed Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning
title_short Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning
title_sort muscarinic and nmda receptors in the substantia nigra play a role in reward-related learning
topic Regular Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850662/
https://www.ncbi.nlm.nih.gov/pubmed/36402549
http://dx.doi.org/10.1093/ijnp/pyac076
work_keys_str_mv AT galajewa muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT barreraeddyd muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT lyncholivial muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT diodatirachel muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT thomasashley muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT schneiderpiper muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT lenhardhayley muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT vashishtapoorva muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning
AT ranaldirobert muscarinicandnmdareceptorsinthesubstantianigraplayaroleinrewardrelatedlearning