The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study

Despite being the most effective treatment for Parkinson's disease, L-DOPA causes a development of dyskinetic movements in the majority of treated patients. L-DOPA-induced dyskinesia is attributed to a dysregulated dopamine transmission within the basal ganglia, but serotonergic and noradrenergic systems are believed to play an important modulatory role. In this study, we have addressed the role of the locus coeruleus nucleus (LC) in a rat model of L-DOPA-induced dyskinesia. Single-unit extracellular recordings in vivo and behavioural and immunohistochemical approaches were applied in rats rendered dyskinetic by the destruction of the nigrostriatal dopamine neurons followed by chronic treatment with L-DOPA. The results showed that L-DOPA treatment reversed the change induced by 6-hydroxydopamine lesions on LC neuronal activity. The severity of the abnormal involuntary movements induced by L-DOPA correlated with the basal firing parameters of LC neuronal activity. Systemic administration of the LC-selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine did not modify axial, limb, and orolingual dyskinesia, whereas chemical destruction of the LC with ibotenic acid significantly increased the abnormal involuntary movement scores. These results are the first to demonstrate altered LC neuronal activity in 6-OHDA lesioned rats treated with L-DOPA, and indicate that an intact noradrenergic system may limit the severity of this movement disorder

Les actes de langage en français: Le compliment dans la communication en ligne

41 p. : il. -- Bibliogr.: p. 40-41Le XXIe siècle est conçu comme le siècle qui a connu les progrès de l’ère numérique et son expansion. Dans le domaine de la technologie, nous pouvons remarquer la croissance massive de l’apparition de dispositifs électroniques, qui sont accompagnés d’avoir accès à Internet de faible coût. Ainsi, ils nous semblait intéressant d’analyser un acte de langage dans un contexte tel que la communication en ligne, qui est de plus en plus fréquent dans notre société. Ce travail constitue une étude autour de l’acte de langage du compliment et son but est de décrire cet acte de langage dans la communication virtuelle. Ainsi, il permet de comparer la communication en ligne, de plus en plus présente de nos jours, avec la communication vis-à-vis. Pour ce faire, cette étude comprend une partie théorique et une partie empirique. Dans la première partie, nous avons effectué un parcours chronologique des différentes théories qui ont étudié l’acte de langage du compliment. Ensuite, la partie empirique consiste en l’analyse d’une suite de compliments réalisés en ligne. Pour effectuer l’analyse de ce corpus, nous avons appliqué une méthodologie spécifique. Les résultats ont permis de montrer des similitudes et des différences dans la réalisation des compliments dans deux contextes différents, comme la communication en ligne et la communication face à face

Cannabinoids and Motor Control of the Basal Ganglia: Therapeutic Potential in Movement Disorders

Cannabinoid receptors in the brain appear to be intimately involved in the motor control. Cannabinoid CB1 receptors are densely located in the basal ganglia (BG), a forebrain system that integrates cortical information to coordinate motor activity regulating signals. In fact, the administration of plant-derived, synthetic or endogenous cannabinoids produces several effects on motor function. These effects are paralleled to changes in the levels of different neurotransmitters in the BG, including GABA, dopamine and glutamate, all of which are important players in movement control

The Role of the Subthalamic Nucleus in L-DOPA Induced Dyskinesia in 6-Hydroxydopamine Lesioned Rats

14 p.L-DOPA is the most effective treatment for Parkinson's disease (PD), but prolonged use leads to disabling motor complications including dyskinesia. Strong evidence supports a role of the subthalamic nucleus (STN) in the pathophysiology of PD whereas its role in dyskinesia is a matter of controversy. Here, we investigated the involvement of STN in dyskinesia, using single-unit extracellular recording, behavioural and molecular approaches in hemi-parkinsonian rats rendered dyskinetic by chronic L-DOPA administration. Our results show that chronic L-DOPA treatment does not modify the abnormal STN activity induced by the 6-hydroxydopamine lesion of the nigrostriatal pathway in this model. Likewise, we observed a loss of STN responsiveness to a single L-DOPA dose both in lesioned and sham animals that received daily L-DOPA treatment. We did not find any correlation between the abnormal involuntary movement (AIM) scores and the electrophysiological parameters of STN neurons recorded 24 h or 20–120 min after the last L-DOPA injection, except for the axial subscores. Nonetheless, unilateral chemical ablation of the STN with ibotenic acid resulted in a reduction in global AIM scores and peak-severity of dyskinesia. In addition, STN lesion decreased the anti-dyskinetogenic effect of buspirone in a reciprocal manner. Striatal protein expression was altered in dyskinetic animals with increases in ΔFosB, phosphoDARPP-32, dopamine receptor (DR) D3 and DRD2/DRD1 ratio. The STN lesion attenuated the striatal molecular changes and normalized the DRD2/DRD1 ratio. Taken together, our results show that the STN plays a role, if modest, in the physiopathology of dyskinesias.This study was supported by grants from the Spanish Ministry of Science SAF 2009-08664 (LU), the department of Industry of the Basque Government S-PE10UN24 (LU and RSP) and Kutxa Obra social (RSP). AA and AS have a fellowship from the University of the Basque Country. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of manuscript

The Effect of 5-HT1A Receptor Agonists on the Entopeduncular Nucleus is Modified in 6-Hydroxydopamine-Lesioned Rats

Background and Purpose l-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l-DOPA-induced dyskinesia, we investigated whether the entopeduncular nucleus is modulated by the 5-HT1A receptor partial and full agonists, buspirone, and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in control and 6-hydroxydopamine (6-OHDA)-lesioned rats with or without long-term l-DOPA treatment. Experimental Approach Extracellular single-unit electrocorticogram and local field potential recordings under anaesthesia, immunostaining assays and optogenetic manipulation coupled to electrophysiological recordings were performed. Key Results Systemic buspirone reduced the entopeduncular nucleus firing rate in the sham animals and burst activity in the 6-OHDA-lesioned rats (with or without l-DOPA treatment), while local administration reduced entopeduncular nucleus activity in all the groups, regardless of DA integrity. Systemic 8-OH-DPAT also induced inhibitory effects only in the sham animals. Effects triggered by buspirone and 8-OH-DPAT were reversed by the 5-HT1A receptor antagonist, WAY-100635. Neither buspirone nor 8-OH-DPAT modified the low-frequency oscillatory activity in the entopeduncular nucleus or its synchronization with the motor cortex. Buspirone did not alter the response induced by subthalamic nucleus opto-stimulation in the entopeduncular nucleus. Conclusion and Implications Systemic 5-HT1A receptor activation elicits different effects on the electrophysiological properties of the entopeduncular nucleus depending on the integrity of the nigrostriatal pathway and it does not alter the relationship between subthalamic nucleus and entopeduncular nucleus neuron activity.Euskal Herriko Unibertsitatea, Grant/Award Number: GIU19/092; Basque Government, Grant/Award Numbers: PIBA 2019-38, T747-13; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: SAF2016-77758-R AEI/FEDER, U

Kannabisaren terapiarako erabilera mugimenduaren asalduretan

Aurkitu ostean egin izan diren ikerkunzek agerian utzi dute endokannabinoideoek funtzio fisiologikoetan duten parte-hartzea. Hain zuzen ere, sistema honen osagaiak (estekatzaile endokannabinoideoak, hartzaileak, biosintesirako eta degradaziorako proteinak) badaude mugimendua kontrolatzen duten garuneko zirkuitu eta nukleoetan (gongoil basaletan) eta ondorioz, parte hartzen dute funtzio motorraren erregulazioan, batez ere dopaminaren maila modulatuz. Bestalde, gongoil basaletan sistema endokannabinoideoan aldaketak deskribatu dira seinale dopaminergikoa gutxitua dagoenean, Parkinsonen gaixotasunean gertatzen den bezala. Horregatik, lanabes berri bezala proposatu da mugimenduaren asaldurak tratatzeko sistema endokannabinoideoaren modulazioa

A Disynaptic Circuit in the Globus Pallidus Controls Locomotion Inhibition

The basal ganglia (BG) inhibit movements through two independent circuits: the striatal neuron-indirect and the subthalamic nucleus-hyperdirect pathways. These pathways exert opposite effects onto external globus pallidus (GPe) neurons, whose functional importance as a relay has changed drastically with the discovery of two distinct cell types, namely the prototypic and the arkypallidal neurons. However, little is known about the synaptic connectivity scheme of different GPe neurons toward both motor-suppressing pathways, as well as how opposite changes in GPe neuronal activity relate to locomotion inhibition. Here, we optogenetically dissect the input organizations of prototypic and arkypallidal neurons and further define the circuit mechanism and behavioral outcome associated with activation of the indirect or hyperdirect pathways. This work reveals that arkypallidal neurons are part of a novel disynaptic feedback loop differentially recruited by the indirect or hyperdirect pathways and that broadcasts inhibitory control onto locomotion only when arkypallidal neurons increase their activity.Analyse électrophysiologique de la dynamique des réseaux des ganglions de la base en situation normale et Parkinsonienne par une approche de manipulation optogénétique sélective de circuit neuronalDiversité neuronale du Globus Pallidus: du profilage moléculaire à la fonction dans le contrôle du mouvementBordeaux Region Aquitaine Initiative for Neuroscienc

Sistema serotonergikoaren eta gongoil basalen arteko elkarrekintza: inplikazio funtzionala eta terapiaren alderdia Parkinsonen gaixotasunean

Serotonina neurotransmisoreak funtzio ezberdinak betetzen ditu informazio-prozesaketaren modulazioan hainbat familiatako hartzaileen aktibazioaren bidez. Hauen artean, erreten ionikoa den hartza ile bat (5-HT3) eta G proteinei lotutako (5-HT1, 5-HT2 , 5-HT4. 7) hartzaileak daude. Neurona serotonergiko gehienak mesentzefaloan kokatuta daude, rafe nukleoetan bereziki . Gongoil basaletara (GB) iristen diren proiekzioak , batez ere dorsal raphe nucleusetik (DRN) heltzen dira. GBak oso ondo antolatuta dauden nukleo subkot1ikalez eratutako sarea da, GB-etako nukleoak striatuma, subthalamic nucleusa (STN), globus pallidusa (barrukoa, GPi eta kanpokoa, GPe) eta substantia nigra (pars compacta, SNc, eta pars reticulata , SNr) direlarik. GBek kontrol motorrean , emozioan eta funtzio kognitiboan parte hartzen dute, eta oso garrantzitsuak dira Parkinsonen Gaixotasunean (PO). Berrikuspen honek serotoninak GBen modulazioan duen funtzioa laburbiltzen du. Bestalde , elkan·ekintza honek PGaren tratamenduan eta L-DOPArebn tratamendu kronikoak eragindako asaldu ra motorretan duen garrantzia eztabaidatzen da