Detection of pantothenic acid-immunoreactive neurons in the rat lateral septal nucleus by a newly developed antibody

Introduction. The available immunohistochemical techniques have documented restricted distribution of vitamins in the mammalian brain. The aim of the study was to develop a highly specific antiserum directed against pantothenic acid to explore the presence of this vitamin in the mammalian brain. Material and methods. According to ELISA tests, the anti-pantothenic acid antiserum used showed a good affinity (10–8 M) and specificity. The antiserum was raised in rabbits. Using an indirect immunoperoxidase technique, the mapping of pantothenic acid-immunoreactive structures was carried out in the rat brain. Results. Pantothenic acid-immunoreactive perikarya were exclusively found in the intermediate part of the lateral septal nucleus. These cells were generally small, round, fusiform or pyramidal and showed 2–3 long (50–100 μm) immunoreactive dendrites. Any immunoreactive axons containing pantothenic acid were detected. Conclusions. The very restricted anatomical distribution of the pantothenic acid suggests that this vitamin could be involved in some specific neurophysiological mechanisms

Generation of specific antisera directed against D-amino acids: focus on the neuroanatomical distribution of D-glutamate and other D-amino acids

This review updates the findings about the anatomical distribution (using immunohistochemical techniques) and possible functions of D-glutamate in the central nervous system of mammals, as well as compares the distribution of D-glutamate with the distribution of the most studied D-amino acids: D-serine and D-aspartate. The protocol used to obtain highly specific antisera directed against D-amino acids is also reported. Immunoreactivity for D-glutamate was found in dendrites and cell bodies, but not in nerve fibers. Perikarya containing D-glutamate were found in the mesencephalon and thalamus. The highest density of cell bodies was found in the dorsal raphe nucleus, the mesencephalic central grey matter, the superior colliculus, and in the subparafascicular thalamic nucleus. In comparison with the distribution of immunoreactive cell bodies containing D-serine or D-aspartate, the distribution of D-glutamate-immunoreactive perikarya is less widespread. Currently, the physiological actions mediated by D-glutamate in the brain are unknown but the restricted neuroanatomical distribution of this D-amino acid suggests that D-glutamate could be involved in very specific physiological mechanisms. In this sense, the possible functional roles of D-glutamate are discussed

Action cellulaire de l'acide rétinoïque et de la triiodothyronine dans le cerveau de souris ou de rats carencés en vitamine A

Des données récentes permettent de faire l'hypothèse qu'une baisse de l'activité de la voie d'action des retinoïdes pourrait générer des altérations de la plasticité synaptique qui participeraient au déclin des capacités mnésiques. L'objectif de notre recherche était d'étudier l'action cellulaire de la vitamine A et des hormones thyroïdiennes dans le cerveau lors d'une carence vitaminique A. Ces "hormones" régulent la transcription génique via leurs récepteurs nucléaires (les RAR, RXR et les TR, respectivement), qui appartiennent à une même famille de protéines transrégulatrices. Dans ce travail, nous avons étudié, dans le cerveau entier mais également dans l'hippocampe, le striatum et le cortex, les conséquences de la carence (i) sur les deux voies de signalisation cellulaire en mesurant l'expression des récepteurs nucléaires, et (ii) sur certains processus neurobiologiques en mesurant l'expression de gènes cibles impliqués dans la plasticité synaptique (la transglutaminase tissulaire, la neurogranine et la neuromoduline). Les principaux résultats obtenus montrent que : - La carence en vitamine A entraîne une diminution de l'expression des récepteurs nucléaires et des gènes cibles dans le cerveau entier et dans le striatum. - L'administration d'acide rétinoïque (AR, métabolite actif de la vitamine A) permet de réactiver uniquement sa propre voie d'action. L'administration de triiodothyronine (T3, forme active des hormones thyroïdiennes) est capable de restaurer l'expression de l'ensemble des gènes étudiés. Ces résultats mettent en évidence l'importance de la voie d'action de la T3 dans les processus adaptatifs qui accompagnent la carence en vitamine A. Plus généralement, ils apportent de nouveaux arguments concernant les interrelations des voies d'action de la vitamine A et des hormones thyroïdiennes.Recent data suggest that hypo-activity of retinoids signalling pathway is involved in synaptic plasticity alterations, which may contribute to memory capacity decline. The aim of our investigation was to study vitamin A and thyroid hormones brain cellular action during vitamin A deficiency. These "hormones" regulate gene transcription through binding their own nuclear receptors (RAR, RXR and TR, respectively), which belong to a same nuclear hormone receptor superfamily. In this work, we have studied in the whole brain but also in the hippocampus, striatum and cortex, the vitamin A deficiency consequences (i) on both signalling pathway by measuring nuclear receptors expression and (ii) on certain neurobiological processes by measuring expression of target genes, which are involved in synaptic plasticity (tissue transglutaminase, neurogranin and neuromodulin). The main results show that: - vitamin A deficiency decreased the expression of nuclear receptors and target genes in the whole brain and in the striatum. - The administration of retinoic acid (RA, the active metabolite of vitamin A) reversed only the RA hypo-signalling. T3 administration was able to restore its own signalling simultaneous with that of vitamin A and the hypoexpression of target genes. These results revealed the importance of T3 signalling in the vitamin A deficiency-related adaptive processes. More generally, they provide new arguments concerning the cross-talk between vitamin A and thyroid hormones pathways signalling.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity

Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R) learning critically depends on the dorsal striatum (DS), spatial memory relies on the hippocampus (HPC). Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA) were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB) within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate) reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments

β4-Nicotinic Receptors Are Critically Involved in Reward-Related Behaviors and Self-Regulation of Nicotine Reinforcement

International audienceNicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster, coding for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChR) subunits, to nicotine addiction. β4*nAChRs have been implicated in nicotine withdrawal, aversion, and reinforcement. Here we show that β4*nAChRs also are involved in non-nicotine-mediated responses that may predispose to addiction-related behaviors. β4 knock-out (KO) male mice show increased novelty-induced locomotor activity, lower baseline anxiety, and motivational deficits in operant conditioning for palatable food rewards and in reward-based Go/No-go tasks. To further explore reward deficits we used intracranial self-administration (ICSA) by directly injecting nicotine into the ventral tegmental area (VTA) in mice. We found that, at low nicotine doses, β4KO self-administer less than wild-type (WT) mice. Conversely, at high nicotine doses, this was reversed and β4KO self-administered more than WT mice, whereas β4-overexpressing mice avoided nicotine injections. Viral expression of β4 subunits in medial habenula (MHb), interpeduncular nucleus (IPN), and VTA of β4KO mice revealed dose- and region-dependent differences: β4*nAChRs in the VTA potentiated nicotine-mediated rewarding effects at all doses, whereas β4*nAChRs in the MHb-IPN pathway, limited VTA-ICSA at high nicotine doses. Together, our findings indicate that the lack of functional β4*nAChRs result in deficits in reward sensitivity including increased ICSA at high doses of nicotine that is restored by re-expression of β4*nAChRs in the MHb-IPN. These data indicate that β4 is a critical modulator of reward-related behaviors.SIGNIFICANCE STATEMENT Human genetic studies have provided strong evidence for a relationship between variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and nicotine addiction. Yet, little is known about the role of β4 nicotinic acetylcholine receptor (nAChR) subunit encoded by this cluster. We investigated the implication of β4*nAChRs in anxiety-, food reward- and nicotine reward-related behaviors. Deletion of the β4 subunit gene resulted in an addiction-related phenotype characterized by low anxiety, high novelty-induced response, lack of sensitivity to palatable food rewards and increased intracranial nicotine self-administration at high doses. Lentiviral vector-induced re-expression of the β4 subunit into either the MHb or IPN restored a "stop" signal on nicotine self-administration. These results suggest that β4*nAChRs provide a promising novel drug target for smoking cessation

From the seismic cycle to long-term deformation: linking seismic coupling and Quaternary coastal geomorphology along the Andean megathrust

International audienceMeasurement of interseismic strain along subduction zones reveals the location of both locked asperities, which might rupture during megathrust earthquakes, and creeping zones, which tend to arrest such seismic ruptures. The heterogeneous pattern of interseismic coupling presumably relates to spatial variations of frictional properties along the subduction interface and may also show up in the fore-arc morphology. To investigate this hypothesis, we compiled information on the extent of earthquake ruptures for the last 500 years and uplift rates derived from dated marine terraces along the South American coastline from central Peru to southern Chile. We additionally calculated a new interseismic coupling model for that same area based on a compilation of GPS data. We show that the coastline geometry, characterized by the distance between the coast and the trench; the latitudinal variations of long-term uplift rates; and the spatial pattern of interseismic coupling are correlated. Zones of faster and long-term permanent coastal uplift, evidenced by uplifted marine terraces, coincide with peninsulas and also with areas of creep on the megathrust where slip is mostly aseismic and tend to arrest seismic ruptures. We conclude that spatial variations of frictional properties along the megathrust dictate the tectono-geomorphological evolution of the coastal zone and the extent of seismic ruptures along strike

From the seismic cycle to long-term deformation: linking seismic coupling and Quaternary coastal geomorphology along the Andean megathrust

International audienceMeasurement of interseismic strain along subduction zones reveals the location of both locked asperities, which might rupture during megathrust earthquakes, and creeping zones, which tend to arrest such seismic ruptures. The heterogeneous pattern of interseismic coupling presumably relates to spatial variations of frictional properties along the subduction interface and may also show up in the fore-arc morphology. To investigate this hypothesis, we compiled information on the extent of earthquake ruptures for the last 500 years and uplift rates derived from dated marine terraces along the South American coastline from central Peru to southern Chile. We additionally calculated a new interseismic coupling model for that same area based on a compilation of GPS data. We show that the coastline geometry, characterized by the distance between the coast and the trench; the latitudinal variations of long-term uplift rates; and the spatial pattern of interseismic coupling are correlated. Zones of faster and long-term permanent coastal uplift, evidenced by uplifted marine terraces, coincide with peninsulas and also with areas of creep on the megathrust where slip is mostly aseismic and tend to arrest seismic ruptures. We conclude that spatial variations of frictional properties along the megathrust dictate the tectono-geomorphological evolution of the coastal zone and the extent of seismic ruptures along strike