Muscarinic and Nicotinic Presynaptic Modulation of EPSCs in the Nucleus Accumbens During Postnatal Development
Notice bibliographique
Résumé
We have studied the modulatory effects of cholinergic agonists on excitatory postsynaptic currents (EPSCs) in nucleus accumbens (nAcb) neurons during postnatal development. Recordings were obtained in slices from postnatal day 1 (P1) to P27 rats using the whole cell patch-clamp technique. EPSCs were evoked by local electrical stimulation, and all experiments were conducted in the presence of bicuculline methchloride in the bathing medium and with QX-314 in the recording pipette. Under these conditions, postsynaptic currents consisted of glutamatergic EPSCs typically consisting of two components mediated by AMPA/kainate (KA) and N-methyl-D-aspartate (NMDA) receptors. The addition of acetylcholine (ACh) or carbachol (CCh) to the superfusing medium resulted in a decrease of 30-60% of both AMPA/KA- and NMDA-mediated EPSCs. In contrast, ACh produced an increase ( approximately 35%) in both AMPA/KA and NMDA receptor-mediated EPSCs when administered in the presence of the muscarinic antagonist atropine. These excitatory effects were mimicked by the nicotinic receptor agonist 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) and blocked by the nicotinic receptor antagonist mecamylamine, showing the presence of a cholinergic modulation mediated by nicotinic receptors in the nAcb. The antagonistic effects of atropine were mimicked by pirenzepine, suggesting that the muscarinic depression of the EPSCs was mediated by M(1)/M(4) receptors. In addition, the inhibitory effects of ACh on NMDA but not on AMPA/KA receptor-mediated EPSC significantly increased during the first two postnatal weeks. We found that, under our experimental conditions, cholinergic agonists produced no changes on membrane holding currents, on the decay time of the AMPA/KA EPSC, or on responses evoked by exogenous application of glutamate in the presence of tetrodotoxin, but they produced significant changes in paired pulse ratio, suggesting that their action was mediated by presynaptic mechanisms. In contrast, CCh produced consistent changes in the membrane and firing properties of medium spiny (MS) neurons when QX-314 was omitted from the recording pipette solution, suggesting that this substance actually blocked postsynaptic cholinergic modulation. Together, these results suggest that ACh can decrease or increase glutamatergic neurotransmission in the nAcb by, respectively, acting on muscarinic and nicotinic receptors located on excitatory terminals. The cholinergic modulation of AMPA/KA and NMDA receptor-mediated neurotransmission in the nAcb during postnatal development could play an important role in activity-dependent developmental processes in refining the excitatory drive on MS neurons by gating specific inputs.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».