The habenula (Hb) is a diencephalic structure that receives substantial input from multiple parts of the limbic system, and communicates with the nucleus interpeduncularis (IPN) by means of the fasciculus retroflexus. The Hb-IPN axis is involved in multiple circuits and subserves a variety of behaviours such as learning and memory, nociception, stress, sleeping and eating. Hb and IPN express all known heteromeric nAChR subunit mRNA transcripts. Furthermore, the results of ligand binding and immunolabeling studies of tissue from WT and KO mice, electrophysiological recordings and neurotransmitter release experiments, suggest that multiple nAChR subtypes are present in these regions. We extracted the heteromeric nAChR subtypes from Hb and IPN of the rat and used immunoprecipitation and sequential immunoprecipitation assays with subunit-specific antibodies to determine their subunit composition. Our data confirm that there are multiple nAChR subtypes in this pathway, including an α3β3β4 subtype that is detected for the first time in the mammalian brain. Immunoprecipitation experiments using IPN and Hb from WT and KO β3 mice showed that the deletion of β3 subunit selectively and markedly decreases the level of α3β4/β2 -containing receptors in the IPN but not in the Hb. The loss of this subtype is paralleled by a decrease in nicotine-elicited 3H-acetylcholine release from IPN synaptosomes. Since the β3 subunit transcript is present in the Hb, but not the IPN, our data on the decrease in number and function of presynaptic α3β4/β2 nAChR in the IPN of β3 KO mice, suggest that the β3 subunit may be necessary to transport this subtype from the Hb to the IPN.
|Titolo:||Nachr subtypes present in the rodent habenulo-interpeduncular pathway and their involvement in 3h-acetylcholine release|
|Data di pubblicazione:||23-apr-2008|
|Citazione:||Nachr subtypes present in the rodent habenulo-interpeduncular pathway and their involvement in 3h-acetylcholine release / C. Gotti, S. Grady, M. Moretti, M. Marks, A. Collins, A. Zanardi, F. Clementi, M. Zoli, L. Pucci. ((Intervento presentato al convegno Nicotinic Acetylcholine Receptors tenutosi a Cambridge nel 2008.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|