7 research outputs found
Requirement of the nicotinic acetylcholine receptor β2 subunit for the anatomical and functional development of the visual system
In the mammalian visual system the formation of eye-specific
layers at the thalamic level depends on retinal waves of spontaneous
activity, which rely on nicotinic acetylcholine receptor activation. We
found that in mutant mice lacking the β2 subunit of the neuronal
nicotinic receptor, but not in mice lacking the α4 subunit,
retinofugal projections do not segregate into eye-specific areas, both
in the dorso-lateral geniculate nucleus and in the superior colliculus.
Moreover, β2−/− mice show an expansion of the binocular subfield
of the primary visual cortex and a decrease in visual acuity at the
cortical level but not in the retina. We conclude that the β2 subunit
of the nicotinic acetylcholine receptor is necessary for the anatomical
and functional development of the visual system
Ultrastructural localization of the α4-subunit of the neuronal acetylcholine nicotinic receptor in the rat substantia nigra
The distribution of the alpha4-subunit of the neuronal nicotinic acetylcholine receptor (nAChR) in the rat brain was examined at light and electron microscopy levels using immunohistochemical staining. In the present study we demonstrate the specificity, in both tissue homogenates and brain sections, of a polyclonal antibody raised against the rat nAChR alpha4-subunit. The characterization of this antibody involved: (1) Western blot analysis of rat brain homogenates and membrane extracts from cells previously transfected with diverse combinations of neuronal nAChR subunits, and (2) immunohistochemistry using transfected cells and rat brain tissue. At the light microscope level, the alpha4-subunit-like-immunoreactivity (LI) was widely distributed in the rat brain and matched the distribution of the alpha4-subunit transcripts observed previously by in situ hybridization. Strong immunohistochemical labeling was detected in the mesencephalic dopaminergic nuclei. The nAChRs in this region are thought to be responsible for the modulation of dopaminergic transmission. The neurotransmitter identity of alpha4-immunolabeled neurons in the substantia nigra pars compacta (SNpc) and the ventral tegmental area was thus assessed by investigating the possible colocalization of the nAChR alpha4-subunit with tyrosine hydroxylase using confocal microscopy. The double labeling experiments unambiguously indicated that the alpha4-subunit-LI is present in dopaminergic neurons. At the electron microscope level, the neurons in the SNpc exhibited alpha4-subunit-LI in association with a minority of postsynaptic densities, suggesting that the alpha4-subunit may be a component of functional nAChRs mediating synaptic transmission between midbrain cholinergic neurons and mesencephalic dopaminergic neurons.This research was supported by grants from The College de France, the Association Française contre la Myopathie, the Council for Tobacco Research, Reynolds
Pharmaceutics, the European Union (Biomed BMH1-CT94–1060 and Biotech 960236), the French Embassy in Spain, the Ministerio de Educacion y Cultura (PB94–0219-CO2-01), the Comunidad de Madrid (AE00268/95), and the National Alliance for Research on Schizophrenia and Depression.Peer reviewe
Reduced antinociception in mice lacking neuronal nicotinic receptor subunits.
Nicotine exerts antinociceptive effects by interacting with one or more of the subtypes of nicotinic acetylcholine receptors (nAChRs) that are present throughout the neuronal pathways that respond to pain. To identify the particular subunits involved in this process, we generated mice lacking the alpha4 subunit of the neuronal nAChR by homologous recombination techniques and studied these together with previously generated mutant mice lacking the beta2 nAChR subunit. Here we show that the homozygous alpha4-/- mice no longer express high-affinity [3H]nicotine and [3H]epibatidine binding sites throughout the brain. In addition, both types of mutant mice display a reduced antinociceptive effect of nicotine on the hot-plate test and diminished sensitivity to nicotine in the tail-flick test. Patch-clamp recordings further reveal that raphe magnus and thalamic neurons no longer respond to nicotine. The alpha4 nAChR subunit, possibly associated with the beta2 nAChR subunit, is therefore crucial for nicotine-elicited antinociception.Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.info:eu-repo/semantics/publishe