Publications associées à Indirect agonist

Striatal Dopamine Signals and Reward Learning

Carl Petersen, Sylvain Crochet, Parviz Ghaderi, Mauro Pulin, Anthony Pierre Robert Renard, Christos Sourmpis, Pol Bech Vilaseca, Meriam Malekzadeh, Robin François Virginien Dard, Yanqi Liu

We are constantly bombarded by sensory information and constantly making decisions on how to act. In order to optimally adapt behavior, we must judge which sequences of sensory inputs and actions lead to successful outcomes in specific circumstances. Neuro ...

Oxford Univ Press2023

Neuromodulation of neocortical microcircuitry: a multi-scale framework to model the effects of cholinergic release

Cristina Colangelo

Neuromodulation of neocortical microcircuits is one of the most fascinating and mysterious aspects of brain physiology. Despite over a century of research, the neuroscientific community has yet to uncover the fundamental biological organizing principles un ...

EPFL2022

Dopamine Transporter, PhosphoSerine129 alpha-Synuclein and alpha-Synuclein Levels in Aged LRRK2 G2019S Knock-In and Knock-Out Mice

Salvatore Novello, Chiara Domenicale

The G2019S mutation in leucine rich-repeat kinase 2 (LRRK2) is a major cause of familial Parkinson's disease. We previously reported that G2019S knock-in mice manifest dopamine transporter dysfunction and phosphoSerine129 alpha-synuclein (pSer129 alpha-syn ...

MDPI2022

Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane

Patrick Daniel Barth, Mahdi Hijazi

The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease(1)and antipsychotic drugs(2). DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine(3), leading to stimulation of G(i) ...

NATURE PUBLISHING GROUP2020

Image-Based Marker-Free Screening of GABA(A) Agonists, Antagonists, and Modulators

Gerardo Turcatti, Benjamin Rappaz, Fabien Kuttler, Damiano Banfi, Pierre Marquet, Pascal Jourdain

The ionotropic GABA(A) receptors represent the main target for different groups of widely used drugs having hypnotic and anxiolytic effects. So far, most approaches used to assess GABA activity involve invasive low -throughput electrophysiological techniqu ...

2019

Estimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in the Neocortex

Henry Markram, Eilif Benjamin Muller, Srikanth Ramaswamy, Rodrigo de Campos Perin, Giuseppe Chindemi, Natali Barros Zulaica

Previous studies based on the 'Quantal Model' for synaptic transmission suggest that neurotransmitter release is mediated by a single release site at individual synaptic contacts in the neocortex. However, recent studies seem to contradict this hypothesis ...

2019

SNAP-Tagged Nanobodies Enable Reversible Optical Control of a G Protein-Coupled Receptor via a Remotely Tethered Photoswitchable Ligand

Kai Johnsson, Johannes Broichhagen, Helen Rebecca Ostlund Farrants

G protein-coupled receptors (GPCRs) mediate the transduction of extracellular signals into complex intracellular responses. Despite their ubiquitous roles in physiological processes and as drug targets for a wide range of disorders, the precise mechanisms ...

AMER CHEMICAL SOC2018

Synaptotagmin2 (Syt2) Drives Fast Release Redundantly with Syt1 at the Output Synapses of Parvalbumin-Expressing Inhibitory Neurons

Ralf Schneggenburger, Olexiy Kochubey, Enida Gjoni, Brice Antoine Alexandre Bouhours

Parvalbumin-expressing inhibitory neurons in the mammalian CNS are specialized for fast transmitter release at their output synapses. However, the Ca2+ sensor(s) used by identified inhibitory synapses, including the output synapses of parvalbumin-expressin ...

2017

A Synaptotagmin Isoform Switch during the Development of an Identified CNS Synapse

Ralf Schneggenburger, Olexiy Kochubey, Zsolt Norbert Babai

Various Synaptotagmin (Syt) isoform genes are found in mammals, but it is unknown whether Syts can function redundantly in a given nerve terminal, or whether isoforms can be switched during the development of a nerve terminal. Here, we investigated the pos ...

2016

An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release Control by Multiple Channels at a CNS Synapse

Henry Markram, Ralf Schneggenburger, Olexiy Kochubey, Felix Schürmann, Yunyun Han, Daniel Keller, Zsolt Norbert Babai

The spatial arrangement of Ca2+ channels and vesicles remains unknown for most CNS synapses, despite of the crucial importance of this geometrical parameter for the Ca2+ control of transmitter release. At a large model synapse, the calyx of Held, transmitt ...

Public Library Science2015

Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release

Ralf Schneggenburger, Olexiy Kochubey, Özgür Genç

Transmitter release at synapses is regulated by preceding neuronal activity, which can give rise to short-term enhancement of release like post-tetanic potentiation (PTP). Diacylglycerol (DAG) and Protein-kinase C (PKC) signaling in the nerve terminal have ...

Elife Sciences Publications Ltd2014

Role of Protein Kinase C and Munc18-1 in a Presynaptic Form of Plasticity, Post-tetanic Potentiation

Özgür Genç

Neurons are arranged in networks in which they communicate between each other by the means of synapses. Synaptic transmission can undergo activity-dependent and short-lived changes in strength, known as short-term synaptic plasticity. Short-term plasticity ...

EPFL2013

Ca2+ channels and transmitter release at the active zone

Ralf Schneggenburger, Olexiy Kochubey, Yunyun Han

Ca2+-dependent transmitter release is the most important signaling mechanism for fast information transfer between neurons. Transmitter release takes places at highly specialized active zones with sub-micrometer dimension, which contain the molecular machi ...

Elsevier2012

Predicting Novel Binding Modes of Agonists to β Adrenergic Receptors Using All-Atom Molecular Dynamics Simulations

Ursula Röthlisberger, Ivano Tavernelli, Marilisa Neri, Stefano Vanni

Understanding the binding mode of agonists to adrenergic receptors is crucial to enabling improved rational design of new therapeutic agents. However, so far the high conformational flexibility of G protein-coupled receptors has been an obstacle to obtaini ...

Public Library of Science2011

Regulation of transmitter release by Ca2+ and synaptotagmin: insights from a large CNS synapse

Ralf Schneggenburger, Olexiy Kochubey

Transmitter release at synapses is driven by elevated intracellular Ca2+ concentration (Ca2+) near the sites of vesicle fusion. Ca2+ signals of profoundly different amplitude and kinetics drive the phasic release component during a presynaptic ac ...

2011

Interaction between Facilitation and Depression at a Large CNS Synapse Reveals Mechanisms of Short-Term Plasticity

Ralf Schneggenburger, Olexiy Kochubey, Martin Guillermo Mueller

The two fundamental forms of short-term plasticity, short-term depression and facilitation, coexist at most synapses, but little is known about their interaction. Here, we studied the interplay between short-term depression and facilitation at calyx of Hel ...

Society for Neuroscience2010

A limited contribution of Ca2+ current facilitation to paired-pulse facilitation of transmitter release at the rat calyx of Held

Ralf Schneggenburger, Martin Guillermo Mueller

Recent studies have suggested that transmitter release facilitation at synapses is largely mediated by presynaptic Ca2+ current facilitation, but the exact contribution of Ca2+ current facilitation has not been determined quantitatively. Here, we determine ...

2008