Brain nicotinic receptors: structure and regulation, role in learning and reinforcement

Changeux, Jean‐Pierre; Bertrand, Daniel; Corringer, Pierre‐Jean; Dehaene, Stanislas; Edelstein, Stuart J.; Léna, Clément; Novère, Nicolas Le; Marubio, Lisa M.; Picciotto, Marina R.; Zoli, Michèle

doi:10.1016/s0165-0173(97)00040-4

Cited by 285 publications

(160 citation statements)

References 145 publications

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“…Anatomical studies suggest that VTA DA cells have high levels of nAChRs [19]. Nicotine affects the dopaminergic system through binding to the nAChR complexes [20], which activates then desensitizes these receptors. The nAChRs are present both on the DAergic cells as well as GABAergic neurons within the VTA.…”

Section: Biological Backgroundmentioning

confidence: 99%

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

Oster

Gutkin

2011

Journal of Physiology-Paris

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The dopaminergic (DA) neurons in the ventral tegmental area (VTA) project to the amygdyla, prefrontal cortex, and the ventral striatum, and are thought to signal reward prediction error. Numerous studies have focused on the tonic and phasic activity of the VTA DAergic neurons as encoding reward related signals. However, recent studies (e.g., [1]) suggest that bursting behavior specifically conveys reward-related information. Moreover, dopamine release during burst firing events is substantially greater than during regular spiking [2]. In addition, DAergic neuronal bursting is influenced by the nicotinic acetycholine receptors (nAChRs) [3,4]. Thus, understanding burst firing is essential when considering VTA neuronal dynamics. Here we introduce a single compartmental model of a VTA DA neuron. We demonstrate that this model captures the essential qualitative behavior of DAergic neuronal dynamics, yet is simple compared to existing, detailed, multi-compartmental models. Moreover, this model could be extended to include the detailed dynamics of two prevalent nAChR subtypes (α4β2 and α7), which is critical to elucidate the role that these receptors play in nicotine addiction.

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Section: Biological Backgroundmentioning

confidence: 99%

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

Oster

Gutkin

2011

Journal of Physiology-Paris

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“…In other cells, 12 'neuronal' nAChR subunit genes encoding a pentameric protein have been identified and designated a2-a10 and b2-b4. [12][13][14][15] Each subunit has four putative transmembrane-spanning domains and a similar topological structure. The a7 and a9 subunits are capable of forming homomeric nAChR channels, which are a-bungarotoxin sensitive.…”

Section: Introductionmentioning

confidence: 99%

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

et al. 2011

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Acetylcholine (ACh) regulates vital functions of T cells by acting on the nicotinic and muscarinic classes of cholinergic receptors, nAChR and mAChRs, respectively. This study was performed in murine splenic T cells. In freshly isolated CD4 and CD8 T cells, we detected mRNAs encoding a5, a9, a10, b1, b2, b4 nAChR subunits and M 1 , M 3 , M 4 and M 5 mAChR subtypes, whereas a2 was detected only in CD8 T cells. In vitro activation of CD4 T cells through T-cell receptor (TCR)/CD3 cross-linking was associated with the appearance of a4 and a7, upregulation of a5, a10, b4, M 1 and M 5 and downregulation of a9 and b2, whereas in vitro activation of CD8 T cells also featured the appearance of a4 and a7, as well as upregulation of a2, a5, b4, M 1 and M 4 , and downregulation of a10, b1, b2 and M 3 . In vitro polarization toward T helper (Th) 1 lineage was associated with a decrease of b2, b4 and M 3 expression; that toward Th2 cells with downregulation of a9 and M 3 , and upregulation of M 1 and M 5 ; and that toward Th17 phenotype with downregulation of a9, a10, b2 and M 3 mAChR. Polarized T cells also expressed a4, but not a1, a2, a3, a6, b3 or M 2 . To determine the role of cholinergic receptors in mediating the immunoregulatory action of autocrine/paracrine ACh, we analyzed the effects of nicotinic and muscarinic agonists ± antagonists on cytokine production in the CD4 þ CD62L þ T cells co-stimulated via TCR/CD3 cross-linking. The nicotinergic stimulation upregulated interferon-g (IFN-g) and downregulated interleukin (IL)-17 secretion, whereas the muscarinic stimulation enhanced IL-10 and IL-17 and inhibited INF-g secretion. These results demonstrated plasticity of the T-cell cholinergic system.

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“…The main nAChRs in the brain are composed of ␣ 4 and ␤ 2 subunits (high affinity for nicotine) or of ␣ 7 subunits only (high affinity for ␣-bungarotoxin) (8). In vitro activation of the latter by low doses of nicotine has been shown to lead to apoptotic cell death of undifferentiated primary and immortalized progenitor cells from the dentate gyrus (DG), the other main region of neurogenesis in the mature brain (9).…”

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confidence: 99%

Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb

Mechawar

Saghatelyan

Grailhe

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Cholinergic axons and nicotinic receptors are abundant in all layers of the olfactory bulb (OB), the main region of newborn neuron integration in the adult brain. Here, we report that the OB granule cell layer in mice lacking the predominant form of brain highaffinity nicotinic acetylcholine receptors (␤ 2 ؊/؊ mice) displayed nearly 50% more newborn neurons and significantly fewer apoptotic cells than did ␤2 ؉/؉ mice. Conversely, in vivo chronic nicotine exposure significantly decreased the number of newborn granule cells in ␤2 ؉/؉ but not ␤2 ؊/؊ adult mice, confirming that the survival of newborn neurons can be controlled by the activation of ␤2-containing nicotinic acetylcholine receptors. Unexpectedly, investigating the behavioral consequence of an increased number of granule cells in ␤2 ؊/؊ mice revealed that these animals have a less robust short-term olfactory memory than their wild-type counterparts. Taken together, these results provide evidence that highaffinity nicotinic receptors are involved in the maturation of adult OB local circuits. They also indicate that an increase in the number of granule cells does not necessarily correlate with better olfactory performance and further highlight the importance of cholinergic afferents for olfactory processing.T hroughout adulthood, the olfactory bulb (OB) is furnished with a constant supply of neuroblasts originating from the subventricular zone (SVZ) and rostral migratory stream (RMS) (1, 2). These cells first migrate tangentially along the RMS before migrating radially in the OB and differentiating into functional inhibitory granule or periglomerular cells (3), a process that takes 3-4 weeks to complete (4, 5). Within the bulb, the activity of these cells can be strongly modulated, via muscarinic (mAChRs) and nicotinic (nAChRs) acetylcholine receptors (6), by the dense cholinergic innervation pervading all OB layers (7).The family of nAChRs is composed of heteromeric and homomeric pentamers forming gated ion channels. The main nAChRs in the brain are composed of ␣ 4 and ␤ 2 subunits (high affinity for nicotine) or of ␣ 7 subunits only (high affinity for ␣-bungarotoxin) (8). In vitro activation of the latter by low doses of nicotine has been shown to lead to apoptotic cell death of undifferentiated primary and immortalized progenitor cells from the dentate gyrus (DG), the other main region of neurogenesis in the mature brain (9). In accordance with these results, in vivo chronic nicotine exposure in adult rats was shown to reduce proliferation in the DG (10, 11). Interestingly, nicotine exposure had no effect on proliferation in the SVZ, suggesting that nAChRs might not be involved in adult OB neurogenesis. However, given the strong expression of high-affinity nAChRs in the OB (12, 13), a study on the involvement of these receptors in events downstream to SVZ proliferation was warranted. In this context, we undertook a study of OB neurogenesis in ␤ 2 Ϫ/Ϫ and ␤ 2 ϩ/ϩ mice subjected or not subjected to chronic nicotine exposure and report here that ␤ 2 -conta...

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Brain nicotinic receptors: structure and regulation, role in learning and reinforcement

Cited by 285 publications

References 145 publications

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb

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