Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system

Swanson, L. W.; Simmons, DM; Whiting, Paul J.; Lindstrom, Jon T.

doi:10.1523/jneurosci.07-10-03334.1987

Cited by 345 publications

(199 citation statements)

References 42 publications

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“…Moderate levels of ␣4 expression were found in the superior colliculus, cerebral cortex, retrosplenial granular cortex, and subiculum. This pattern agrees well with previous data (Swanson et al, 1987;Marks et al, 1992;Whiteaker et al, 2006). When ␣4YFP fluorescence is totaled for these 16 brain regions, the Het mouse brain fluorescence is approximately one-half (45%) that of Hom, consistent with straightforward gene dosage.…”

Section: Characterizing the ␣4yfp Mice: Normal Nicotinic Receptor Funsupporting

confidence: 92%

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Nashmi

Xia²,

Deshpande³

et al. 2007

J. Neurosci.

247

320

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Understanding effects of chronic nicotine requires identifying the neurons and synapses whose responses to nicotine itself, and to endogenous acetylcholine, are altered by continued exposure to the drug. To address this problem, we developed mice whose ␣4 nicotinic receptor subunits are replaced by normally functioning fluorescently tagged subunits, providing quantitative studies of receptor regulation at micrometer resolution. Chronic nicotine increased ␣4 fluorescence in several regions; among these, midbrain and hippocampus were assessed functionally. Although the midbrain dopaminergic system dominates reward pathways, chronic nicotine does not change ␣4* receptor levels in dopaminergic neurons of ventral tegmental area (VTA) or substantia nigra pars compacta. Instead, upregulated, functional ␣4* receptors localize to the GABAergic neurons of the VTA and substantia nigra pars reticulata. In consequence, GABAergic neurons from chronically nicotine-treated mice have a higher basal firing rate and respond more strongly to nicotine; because of the resulting increased inhibition, dopaminergic neurons have lower basal firing and decreased response to nicotine. In hippocampus, chronic exposure to nicotine also increases ␣4* fluorescence on glutamatergic axons of the medial perforant path. In hippocampal slices from chronically treated animals, acute exposure to nicotine during tetanic stimuli enhances induction of long-term potentiation in the medial perforant path, showing that the upregulated ␣4* receptors in this pathway are also functional. The pattern of cell-specific upregulation of functional ␣4* receptors therefore provides a possible explanation for two effects of chronic nicotine: sensitization of synaptic transmission in forebrain and tolerance of dopaminergic neuron firing in midbrain.

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Section: Characterizing the ␣4yfp Mice: Normal Nicotinic Receptor Funsupporting

confidence: 92%

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Nashmi

Xia²,

Deshpande³

et al. 2007

J. Neurosci.

247

320

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“…The SNc DA neurons receive cholinergic input from the pedunculopontine nucleus (Lichtensteiger et al, 1982;Clarke et al, 1985;Swanson et al, 1987;Bolam et al, 1991). Both AChE and nAChRs are expressed in SNc (Henderson and Greenfield, 1984;Emmett and Greenfield, 2005).…”

Section: Discussionmentioning

confidence: 99%

Mefloquine Enhances Nigral γ-Aminobutyric Acid Release via Inhibition of Cholinesterase

Zhou

Xia²,

McArdle³

et al. 2006

J Pharmacol Exp Ther

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Mefloquine, a widely used antimalarial drug, has many neuropsychiatric effects. Although the mechanisms underlying these side effects remain unclear, recent studies show that mefloquine enhances spontaneous transmitter release and inhibits cholinesterases. In this study, we examined the effect of mefloquine on GABA receptor-mediated, spontaneous inhibitory postsynaptic currents (sIPSCs) of dopaminergic neurons, mechanically dissociated from the substantia nigra pars compacta of rats aged 6 to 17 postnatal days. Mefloquine (0.1-10 M) robustly and reversibly increased the frequency of sIPSCs with an EC 50 of 1.3 M. Mefloquine also enhanced the frequency of miniature inhibitory postsynaptic currents in the presence of tetrodotoxin but without changing their mean amplitude. This suggests that mefloquine acts presynaptically to increase GABA release. Mefloquine-induced enhancement of sIPSCs was significantly attenuated in medium containing low Ca 2ϩ (0.5 mM) or following pretreatment with 1,2-bis (2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid tetrakis(acetoxymethyl ester (30 M), a membrane-permeable Ca 2ϩ chelator. In contrast, 100 M Cd 2ϩ did not alter the action of mefloquine. This suggests that mefloquine-induced facilitation of GABA release depends on extracellular and intraterminal Ca 2ϩ but not on voltage-gated Ca 2ϩ channels. Mefloquine-induced enhancement of sIPSCs was significantly attenuated in the presence of the anticholinesterase agent physostigmine or blockers of non-␣7 nicotinic acetylcholine receptors. Taken together, these data suggest that mefloquine enhances GABA release through its inhibition of cholinesterase. This allows accumulation of endogenously released acetylcholine, which activates neuronal nicotinic receptors on GABAergic nerve terminals. The resultant increase of Ca 2ϩ entry into these terminals enhances vesicular release of GABA. This action may contribute to the neurobehavioral effects of mefloquine.

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“…In comparison to other areas of the thalamus, cholinoreceptors, and high affinity, choline-uptake sites as identified immunocytochemically or in radioligand binding studies appeared to us rather weakly labeled in the midline-intralaminar complex, as compared to the higher densities in neighboring areas of the diencephalon, for example, reticular and anterior thalamic nuclear groups (Clarke et al, 1985;Quirion, 1987;see Fig. 20 of Swanson et al, 1987). The midline-intralaminar complex was also unlabeled by irz situ RNA hybridization of an a-subunit probe for the neural nicotinic-ACh receptor (Goldman et al, 1986).…”

Section: Nadphdmentioning

confidence: 94%

Monoamines and nitric oxide are employed by afferents engaged in midline thalamic regulation

Otake

Ruggiero

1995

J. Neurosci.

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The neurochemical identities of afferents to the midline thalamus were investigated in chloral hydrate-anesthetized adult Sprague-Dawley rats. The retrograde tracers, FluoroGold or cholera toxin B subunit, were centered on the paraventricular thalamic nucleus (n.Pvt), a periventricular member of the diffuse thalamocortical projection system that is reciprocally linked with visceral areas of cerebral cortex and implicated in food intake and addictive behavior. Tissues were processed with antisera raised against 5-HT, the catecholamine- synthesizing enzymes, tyrosine hydroxylase or phenylethanolamine N- methyltransferase or the cholinergic anabolic enzyme, ChAT. Serotonergic afferents principally derive from dorsal and median constituents of the mesopontine raphe. Previously unrecognized sources of catecholaminergic afferents were detected. Adrenergic afferents were traced to neurons in the C1 and C3 areas of rostral medullary reticular formation and periventricular gray, respectively, and the C2 area corresponding to the dorsal general viscerosensory field of nucleus tractus solitarii. Noradrenergic afferents arise principally from neurons in the locus ceruleus and A5 area. Dopaminergic projections to the n.Pvt derive from the A14, A13 and A11 cell groups in diencephalon. Afferents presumed to generate nitric oxide (NO) as a diffusible membrane-permeant transcellular signal were detected by processing retrogradely labeled tissues histochemically for NADPH-diaphorase, a molecule associated with nitric oxide synthase. NO in the n.Pvt is generated predominantly by noncholinergic neurons in the lateral hypothalamic area and mesopontine tegmentum. In striking contrast, extensive interactions were predicted between NO and ACh in the central medial and other loci in the nondiscriminative thalamus. We conclude that the n.Pvt is a site of interaction of NO and monoaminergic afferents derived from nuclei implicated in sensory gating, regulation of electrocortical neural activity and behavior. Taken collectively, our data predict that the labile transcellular messenger NO may enable structurally differentiated subnuclei of the diffuse thalamocortical projection system to act in concert as a functionally unified unit.

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Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system

Cited by 345 publications

References 42 publications

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Mefloquine Enhances Nigral γ-Aminobutyric Acid Release via Inhibition of Cholinesterase

Monoamines and nitric oxide are employed by afferents engaged in midline thalamic regulation

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