16 research outputs found
Behavioral Sequence Analysis Reveals a Novel Role for Ă2* Nicotinic Receptors in Exploration
Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the
central nervous system and modulate neuronal function in most mammalian brain
structures. The contribution of defined nAChR subunits to a specific behavior is
thus difficult to assess. Mice deleted for Ă2-containing nAChRs
(Ă2â/â) have been shown to be hyperactive in an
open-field paradigm, without determining the origin of this hyperactivity. We
here develop a quantitative description of mouse behavior in the open field
based upon first order Markov and variable length Markov chain analysis focusing
on the time-organized sequence that behaviors are composed of. This description
reveals that this hyperactivity is the consequence of the absence of specific
inactive states or âstopsâ. These stops are associated with
a scanning of the environment in wild-type mice (WT), and they affect the way
that animals organize their sequence of behaviors when compared with stops
without scanning. They characterize a specific âdecision
momentâ that is reduced in Ă2â/â mutant
mice, suggesting an important role of Ă2-nAChRs in the strategy used
by animals to explore an environment and collect information in order to
organize their behavior. This integrated analysis of the displacement of an
animal in a simple environment offers new insights, specifically into the
contribution of nAChRs to higher brain functions and more generally into the
principles that organize sequences of behaviors in animals
Novel Strains of Mice Deficient for the Vesicular Acetylcholine Transporter: Insights on Transcriptional Regulation and Control of Locomotor Behavior
Defining the contribution of acetylcholine to specific behaviors has been challenging, mainly because of the difficulty in generating suitable animal models of cholinergic dysfunction. We have recently shown that, by targeting the vesicular acetylcholine transporter (VAChT) gene, it is possible to generate genetically modified mice with cholinergic deficiency. Here we describe novel VAChT mutant lines. VAChT gene is embedded within the first intron of the choline acetyltransferase (ChAT) gene, which provides a unique arrangement and regulation for these two genes. We generated a VAChT allele that is flanked by loxP sequences and carries the resistance cassette placed in a ChAT intronic region (FloxNeo allele). We show that mice with the FloxNeo allele exhibit differential VAChT expression in distinct neuronal populations. These mice show relatively intact VAChT expression in somatomotor cholinergic neurons, but pronounced decrease in other cholinergic neurons in the brain. VAChT mutant mice present preserved neuromuscular function, but altered brain cholinergic function and are hyperactive. Genetic removal of the resistance cassette rescues VAChT expression and the hyperactivity phenotype. These results suggest that release of ACh in the brain is normally required to âturn downâ neuronal circuits controlling locomotion
Albert Dufourcq. L'avenir du christianisme
Maubourguet J. Albert Dufourcq. L'avenir du christianisme. In: Revue d'histoire de l'Ăglise de France, tome 19, n°84, 1933. pp. 375-377
Albert Dufourcq. L'avenir du christianisme
Maubourguet J. Albert Dufourcq. L'avenir du christianisme. In: Revue d'histoire de l'Ăglise de France, tome 19, n°84, 1933. pp. 375-377
MĂ©langes Albert Dufourcq
Maubourguet J. MĂ©langes Albert Dufourcq. In: Revue d'histoire de l'Ăglise de France, tome 18, n°81, 1932. pp. 496-500
MĂ©langes Albert Dufourcq
Maubourguet J. MĂ©langes Albert Dufourcq. In: Revue d'histoire de l'Ăglise de France, tome 18, n°81, 1932. pp. 496-500
Two-dimensional free surface flow numerical model for vertical slot fishways
Numerical results of a vertical slot fishway study are presented. The Saint-Venant equations are solved using TELEMAC-2D. Turbulence modelling uses the classical two equations k-epsilon closure model. A comparison with velocity measurements performed at the Laboratoire d'Etudes Aerodynamiques of University of Poitiers, France, using particle image velocimetry and acoustic Doppler velocimetry permitted to validate numerical results. Turbulence modelling is required not only to have a fish-friendly flow but, more remarkably, by the fact that taking a constant eddy viscosity model gives incorrect mean flow patterns. Three longitudinal slopes were tested. The validity of the k-epsilon closure model is discussed. Special attention was paid to the calculated turbulent kinetic energy and the energy dissipation rate. This last parameter is of great interest because its spatial distribution significantly affects the progress relative to fish passage efficiency
Methodological issues in the non pharmacological treatment of BPSD in nursing home â the TNM study â
Distinct contributions of nicotinic acetylcholine receptor subunit α4 and subunit α6 to the reinforcing effects of nicotine
Nicotine is the primary psychoactive component of tobacco. Its reinforcing and addictive properties depend on nicotinic acetylcholine receptors (nAChRs) located within the mesolimbic axis originating in the ventral tegmental area (VTA). The roles and oligomeric assembly of subunit α4- and subunit α6-containing nAChRs in dopaminergic (DAergic) neurons are much debated. Using subunit-specific knockout mice and targeted lentiviral re-expression, we have determined the subunit dependence of intracranial nicotine self-administration (ICSA) into the VTA and the effects of nicotine on dopamine (DA) neuron excitability in the VTA and on DA transmission in the nucleus accumbens (NAc). We show that the α4 subunit, but not the α6 subunit, is necessary for ICSA and nicotine-induced bursting of VTA DAergic neurons, whereas subunits α4 and α6 together regulate the activity dependence of DA transmission in the NAc. These data suggest that α4-dominated enhancement of burst firing in DA neurons, relayed by DA transmission in NAc that is gated by nAChRs containing α4 and α6 subunits, underlies nicotine self-administration and its long-term maintenance
Critical Dynamics in Host-Pathogen Systems
International audienceHost-pathogen interactions provide a fascinating example of two or more active genomes directly exerting mutual influence upon each other. These encounters can lead to multiple outcomes from symbiotic homeostasis to mutual annihilation, undergo multiple cycles of latency and lysogeny, and lead to coevolution of the interacting genomes. Such systems pose numerous challenges but also some advantages to modeling, especially in terms of functional, mathematical genome representations. The main challenges for the modeling process start with the conceptual definition of a genome for instance in the case of host-integrated viral genomes. Furthermore, hardly understood influences of the activity of either genome on the other(s) via direct and indirect mechanisms amplify the needs for a coherent description of genome activity. Finally, genetic and local environmental heterogeneities in both the host's cellular and the pathogen populations need to be considered in multiscale modeling efforts. We will review here two prominent examples of host-pathogen interactions at the genome level, discuss the current modeling efforts and their shortcomings, and explore novel ideas of representing active genomes which promise being particularly adapted to dealing with the modeling challenges posed by host-pathogen interactions