scholarly journals Nicotinic modulation of hierarchal inhibitory control over prefrontal cortex resting state dynamics: modeling of genetic modification and schizophreniarelated pathology

2018 ◽  
Author(s):  
Marie Rooy ◽  
Fani Koukouli ◽  
Uwe Maskos ◽  
Boris Gutkin
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Activity Patterns ◽  
Genetic Mutation ◽  
Inhibitory Neurons ◽  
Dynamics Modeling ◽  
Single Nucleotide ◽  
Chronic Nicotine ◽  
Firing Rate Models ◽  
Activity State

AbstractNicotinic acetylcholine receptors (nAChRs) strongly modulate the cholinergic drive to a hierarchy of inhibitory neurons in the superficial layers of the PFC, critical to cognitive processes. Genetic deletion of various types of nAChRs, located on specific interneurons, impacts the properties of ultra-slow transitions between high and low activity states (H-states and L-states, respectively), recorded in mice during quiet wakefulness. In addition, recent data indicate that a genetic mutation of the α5 nAChR subunit located on vasoactive intestinal polypeptide (VIP) inhibitory neurons, the rs16969968 single nucleotide polymorphism (α5 SNP), appears to be responsible for “hypofrontality” observed in schizophrenia. Chronic nicotine application to α5 SNP mice restores neural activity to control levels. Using firing rate models of hierarchically organized neural populations, we showed that the change of activity patterns recorded in the genetically modified mice can be explained by a change of activity state stability, differentially modulated by cholinergic inputs to parvalbumin (PV), somatostatin (SOM) or VIP inhibitory populations. A change in amplitude, but not duration of H-states fully account for the lowered pyramidal (PYR) firing rates recorded in α5 SNP mice. We demonstrate that desensitization and upregulation of β2 nAChRs located on SOM interneurons, but not activation of α5 nAChRs located on VIP interneurons, by chronic nicotine application could account for activity normalization recorded in α5 SNP mice. The model implies that subsequent nicotine withdrawal should lead to PYR activity depression more severe than the original hypofrontality caused by SNP mutation.

scholarly journals α6β2*-subtype nicotinic acetylcholine receptors are more sensitive than α4β2*-subtype receptors to regulation by chronic nicotine administration

2014 ◽  
Vol 130 (2) ◽  
pp. 185-198 ◽  
Author(s):  
Michael J. Marks ◽  
Sharon R. Grady ◽  
Outi Salminen ◽  
Miranda A. Paley ◽  
Charles R. Wageman ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Chronic Nicotine ◽  
Nicotine Administration

scholarly journals Neonicotinoids can cause arrested pupal ecdysis in Lepidoptera

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niranjana Krishnan ◽  
Russell A. Jurenka ◽  
Steven P. Bradbury
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Helicoverpa Zea ◽  
Galleria Mellonella ◽  
Danaus Plexippus ◽  
Monarch Butterfly ◽  
Corn Earworm ◽  
Inhibitory Neurons ◽  
Corn Borers ◽  
Delayed Initiation

AbstractRecently, we reported a novel mode of action in monarch butterfly (Danaus plexippus) larvae exposed to neonicotinoid insecticides: arrest in pupal ecdysis following successful larval ecdysis. In this paper, we explore arrested pupal ecdysis in greater detail and propose adverse outcome pathways to explain how neonicotinoids cause this effect. Using imidacloprid as a model compound, we determined that final-instar monarchs, corn earworms (Helicoverpa zea), and wax moths (Galleria mellonella) showed high susceptibility to arrested pupal ecdysis while painted ladies (Vanessa cardui) and red admirals (Vanessa atalanta) showed low susceptibility. Fall armyworms (Spodoptera frugiperda) and European corn borers (Ostrinia nubilalis) were recalcitrant. All larvae with arrested ecdysis developed pupal cuticle, but with incomplete shedding of larval cuticle and unexpanded pupal appendages; corn earworm larvae successfully developed into adults with unexpanded appendages. Delayed initiation of pupal ecdysis was also observed with treated larvae. Imidacloprid exposure was required at least 26 h prior to pupal ecdysis to disrupt the molt. These observations suggest neonicotinoids may disrupt the function of crustacean cardioactive peptide (CCAP) neurons, either by directly acting on their nicotinic acetylcholine receptors or by acting on receptors of inhibitory neurons that regulate CCAP activity.

Nicotinic Acetylcholine Receptors in Glucose Homeostasis: The Acute Hyperglycemic and Chronic Insulin-Sensitive Effects of Nicotine Suggest Dual Opposing Roles of the Receptors in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3793-3805 ◽  
Author(s):  
Christine U. Vu ◽  
Jawed A. Siddiqui ◽  
Paul Wadensweiler ◽  
Jiaur R. Gayen ◽  
Ennio Avolio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotine Exposure ◽  
Dependent Manner ◽  
Nicotinic Acetylcholine ◽  
Nicotine Treatment ◽  
Chronic Nicotine ◽  
Chronic Nicotine Treatment

Abstract Cigarette smoking causes insulin resistance. However, nicotine induces anti-inflammation and improves glucose tolerance in insulin-resistant animal models. Here, we determined the effects of nicotine on glucose metabolism in insulin-sensitive C57BL/J6 mice. Acute nicotine administration (30 min) caused fasting hyperglycemia and lowered insulin sensitivity acutely, which depended on the activation of nicotinic-acetylcholine receptors (nAChRs) and correlated with increased catecholamine secretion, nitric oxide (NO) production, and glycogenolysis. Chlorisondamine, an inhibitor of nAChRs, reduced acute nicotine-induced hyperglycemia. qRT-PCR analysis revealed that the liver and muscle express predominantly β4 > α10 > α3 > α7 and β4 > α10 > β1 > α1 mRNA for nAChR subunits respectively, whereas the adrenal gland expresses β4 > α3 > α7 > α10 mRNA. Chronic nicotine treatment significantly suppressed expression of α3-nAChR (predominant peripheral α-subunit) in liver. Whereas acute nicotine treatment raised plasma norepinephrine (NE) and epinephrine (Epi) levels, chronic nicotine exposure raised only Epi. Acute nicotine treatment raised both basal and glucose-stimulated insulin secretion (GSIS). After chronic nicotine treatment, basal insulin level was elevated, but GSIS after acute saline or nicotine treatment was blunted. Chronic nicotine exposure caused an increased buildup of NO in plasma and liver, leading to decreased glycogen storage, along with a concomitant suppression of Pepck and G6Pase mRNA, thus preventing hyperglycemia. The insulin-sensitizing effect of chronic nicotine was independent of weight loss. Chronic nicotine treatment enhanced PI-3-kinase activities and increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation in an nAChR-dependent manner coupled with decreased cAMP response element–binding protein (CREB) phosphorylation. The latter effects caused suppression of Pepck and G6Pase gene expression. Thus, nicotine causes both insulin resistance and insulin sensitivity depending on the duration of the treatment.

scholarly journals Nicotine exploits a COPI-mediated process for chaperone-mediated up-regulation of its receptors

2013 ◽  
Vol 143 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Brandon J. Henderson ◽  
Rahul Srinivasan ◽  
Weston A. Nichols ◽  
Crystal N. Dilworth ◽  
Diana F. Gutierrez ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Resonance Energy ◽  
High Sensitivity ◽  
Brain Regions ◽  
Substantia Nigra Pars Compacta ◽  
Common Mechanism ◽  
Binding Motif ◽  
Chronic Nicotine ◽  
Dependent Process

Chronic exposure to nicotine up-regulates high sensitivity nicotinic acetylcholine receptors (nAChRs) in the brain. This up-regulation partially underlies addiction and may also contribute to protection against Parkinson’s disease. nAChRs containing the α6 subunit (α6* nAChRs) are expressed in neurons in several brain regions, but comparatively little is known about the effect of chronic nicotine on these nAChRs. We report here that nicotine up-regulates α6* nAChRs in several mouse brain regions (substantia nigra pars compacta, ventral tegmental area, medial habenula, and superior colliculus) and in neuroblastoma 2a cells. We present evidence that a coat protein complex I (COPI)-mediated process mediates this up-regulation of α6* or α4* nAChRs but does not participate in basal trafficking. We show that α6β2β3 nAChR up-regulation is prevented by mutating a putative COPI-binding motif in the β3 subunit or by inhibiting COPI. Similarly, a COPI-dependent process is required for up-regulation of α4β2 nAChRs by chronic nicotine but not for basal trafficking. Mutation of the putative COPI-binding motif or inhibition of COPI also results in reduced normalized Förster resonance energy transfer between α6β2β3 nAChRs and εCOP subunits. The discovery that nicotine exploits a COPI-dependent process to chaperone high sensitivity nAChRs is novel and suggests that this may be a common mechanism in the up-regulation of nAChRs in response to chronic nicotine.

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