Drug-Driven AMPA Receptor Redistribution Mimicked by Selective Dopamine Neuron Stimulation

Addictive drugs have in common that they cause surges in dopamine (DA) concentration in the mesolimbic reward system and elicit synaptic plasticity in DA neurons of the ventral tegmental area (VTA). Cocaine for example drives insertion of GluA2-lacking AMPA receptors (AMPARs) at glutamatergic synapes in DA neurons. However it remains elusive which molecular target of cocaine drives such AMPAR redistribution and whether other addictive drugs (morphine and nicotine) cause similar changes through their effects on the mesolimbic DA system

MAD magazine et la société américaine

MAD magazine et la société américain

Activité électrophysiologique des neurones dopaminergiques chez le rat non-anesthésié (influence du cycle veille/sommeil, de la stimulation du cortex préfrontal et de la sensibilisation à l'amphétamine)

Les neurones dopaminergiques de l'aire tegmentale ventrale (ATV) et leurs afférences en provenance du cortex préfrontal (CPF) sont impliqués dans la physiopathologie de l'addiction. A l'aide d'enregistrements électrophysiologiques des neurones de l'ATV chez le rat vigile en contention stéréotaxique, nous avons montré i) que contrairement à un dogme vieux de 20 ans, l'activité spontanée des neurones DA de l'ATV varie au cours du cycle veille sommeil et augmente fortement en sommeil paradoxal, ii) que la voie directe monosynaptique CPF-ATV n'induit que peu ou pas de bouffées de potentiels d'action et est fortement inhibée par les anesthésiques, iii) que l'administration d'amphétamine induisant une sensibilisation ne modifie, dans nos conditions expérimentales, ni l'activité spontanée des neurones DA pendant l'éveil, ni leur réactivité à la stimulation du CPF. Ce travail nous a permis de démontrer l'implication des neurones DA de l'ATV dans la physiologie du sommeil paradoxal, siège de l'activité onirique, et de préciser l'infuluence du CPF sur la VTA. Il semble également surggérer que le rôle joué par cette afférence glutamatergique dans les mécanismes responsables de la sensibilisation à l'amphétamine ait été jusqu'alors surestiméLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Age-related memory decline, dysfunction of the hippocampus and therapeutic opportunities

International audienc

Biostability Assessment of Flexible Parylene C-based Implantable Sensor in Wireless Chronic Neural Recording

International audienceThe stability of polymer-based sensors in a biological environment remains a challenge, as delamination and swelling often compromise mechanical and electrical capability. We have developed a neural implant based on Parylene C, a biocompatible flexible polymer, with PEDOT-nanostructured gold patterns to record the brain electrical activity. Here, we show first evidence of device biostability through in vitro soaking tests in artificial brain environment and in vivo recording in mice. Our results indicate that after over the six months trial, more than 75% of the in vitro electrodes have stable impedance, and the implanted sensors in mice were able to accurately record signals from mice hippocampi. None of the implants presented with signs of Parylene degradation or metal corrosion. Overall, the devices are promising candidates for reliable, chronically implanted sensors in the biomedical field

Parylene-based flexible neural probes with PEDOT coated surface for brain stimulation and recording

International audienceImplantable neural prosthetics devices offer a promising opportunity for the restoration of lost functions in patients affected by brain or spinal cord injury, by providing the brain with a non-muscular channel able to link machines to the nervous system. Nevertheless current neural microelectrodes suffer from high initial impedance and low charge-transfer capacity because of their small-feature geometry (Abidian et al., 2010; Cui and Zhou, 2007). In this work we have developed PEDOT-modified neural probes based on flexible substrate capable to answer to the three critical requirements for neuroprosthetic device: efficiency, lifetime and biocompatibility. We propose a simple procedure for the fabrication of neural electrodes fully made of Parylene-C, followed by an electropolymerization of the active area with the conductive polymer PEDOT that is shown to greatly enhance the electrical performances of the device. In addition, the biocompatibility and the very high SNR exhibited during signal recording make our device suitable for long-term implantation

In vitro and in vivo biostability assessment of chronically-implanted Parylene C neural sensors

International audienceParylene C has rapidly gained attention as a exible biomaterial for a new generation of chronic neural probes. However, polymeric material failure in the form of delamination, swelling or tearing, often compromises device biostability in the long term. This work constitutes a rst step towards lifetime assessment of Parylene C implanted devices. We have conceived a Parylene C-based neural probe with PEDOT-nanostructured gold electrodes for the recording of brain activity. The material response to its biological environment was studied through in vitro soaking tests and in vivo wireless recordings in mice brain, both carried out for up to 6 months. Impedance monitoring and SEM images indicate that over the length of this trial, none of the implants presented with apparent signs of material degradation. Packaging reliability was a predominant factor in device failure, with a certain number of faulty connection appearing over time. This parameter aside, all soaked devices were stable in Articial Cerebro-Spinal Fluid, with impedances within 10% of their initial value after 6 months at 37°C. Besides, at least 70% of the implanted device were able to accurately record wirelessly high amplitude hippocampal Local Field Potentials from freely-moving mice, with steady Signal-to-Noise Ratio. In other terms, Parylene C implantable sensors responded minimally to articial and actual physiological conditions during a period of 6 months, which makes them promising candidates for reliable, chronically implanted sensors in the biomedical eld

D1/5 dopamine receptors are necessary for learning a novel context

International audienceDopamine participates in encoding memories and could either encode rewarding/aversive value of unconditioned stimuli or act as a novelty signal triggering contextual learning. Here we show that intraperitoneal injection of the dopamine D1/5R antagonist SCH23390 impairs contextual fear conditioning and tone-shock association, while intrahippocampal injection only impairs contextual fear conditioning. By using the context pre-exposure facilitation effect test, we show that SCH23390 is able to block the encoding of the context during the pre-exposure phase. Thus, we provide additional evidence that dopamine is involved in encoding conjunctive representations of new contexts

Early disruption of parvalbumin expression and perineuronal nets in the hippocampus of the Tg2576 mouse model of Alzheimer's disease can be rescued by enriched environment

International audienc

Early Onset of Hypersynchronous Network Activity and Expression of a Marker of Chronic Seizures in the Tg2576 Mouse Model of Alzheimer’s Disease

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