Biology subjects

Tricoire, L.

Publications and source records attributed to Tricoire, L..

4 recordsLinked to original sources

bioRxiv2023

Voltage tunes mGlu5 receptor function, impacting synaptic transmission

Voltage sensitivity is a common feature of many membrane proteins, including some G-protein coupled receptors (GPCRs). However, the functional consequences of voltage sensitivity in GPCRs are not well understood. In this study, we investigated the voltage sensitivity of the post-synaptic metabotropic glutamate receptor mGlu5 and its impact on synaptic transmission. Using biosensors and electrophysiological recordings in non-excitable HEK293T cells or neurons, we found that mGlu5 receptor function is optimal at resting membrane potentials. We observed that membrane depolarization significantly reduced mGlu5 receptor activation, Gq-PLC/PKC stimulation, Ca2+ release, and mGlu5 receptor-gated currents through TRPC6 channels or NMDA receptors. Notably, we report a previously unknown activity of the NMDA receptor at the resting potential of neurons, enabled by mGlu5. Our findings suggest that mGlu5 receptor activity is directly regulated by membrane voltage which may have a significant impact on synaptic processes and pathophysiological functions.

neuroscience↗

bioRxiv2022

Self-generation of goal-directed choices in a distributed dopaminergic andprefrontal circuit

Goal-directed choices that are not triggered by external cues arise from internal representations of the outcomes. The use of a stimulus to specify when to act, which option to take, or whether to explore, has led to consider the reward circuit as a feedforward set of modules carrying independent computations. Here, we develop an uncued task in which mice self-determine the initiation, direction, vigor and pace of their actions based on their knowledge of the outcomes. Using electrophysiological recordings, pharmacology and optogenetics, we identify a sequence of oscillations and firing in the ventral tegmental area (VTA), orbitofrontal (OFC) and prefrontal cortices (PFC) that co-encodes and co-determines self-initiation and choices. This sequence appeared with learning as an unguided realignment of spontaneous dynamics. The interactions between the structures depended on the reward context, in particular regarding the uncertainty associated with the different options. We suggest that self-generated choices arise from a distributed circuit based on an OFC-VTA core setting whether to wait or to initiate actions, while the PFC is specifically engaged by reward uncertainty to participate in both the selection and pace of actions. HighlightsO_LISelf-paced actions arise from contextual reorganization of mesocortical dynamics. C_LIO_LIVTA, PFC and OFC complementarily encode predictions and errors about outcomes. C_LIO_LIDistributed firing-then-oscillations dynamics set the goal, initiation and pace of actions. C_LIO_LIVTA and PFC antagonistically promote and inhibit motivation by reward uncertainty. C_LI

neuroscience↗

bioRxiv2020

Probing the ionotropic activity of the orphan glutamate delta 2 receptor with genetically-engineered photopharmacology.

Glutamate delta (GluD) receptors belong to the ionotropic glutamate receptor family, yet whether they actually form functional and physiologically-relevant ion channels in neurons remains a debated question. Here we used a chemo-genetic approach to engineer specific and photo-reversible pharmacology in the orphan GluD2 receptor. We incorporated a cysteine mutation in the cavity located above the putative ion channel pore, for site-specific conjugation with a photoswitchable ligand. We first showed that, in the constitutively-open GluD2 Lurcher mutant, current could be rapidly and reversibly decreased with light. We then transposed the cysteine mutation to the native receptor, to demonstrate with absolute pharmacological specificity that metabotropic glutamate receptor signaling opens the GluD2 ion channel in heterologous expression system. Our results assess the functional relevance of GluD2 ion channel and introduce an optogenetic tool that will provide a novel and powerful means for probing GluD2 ionotropic contribution to neuronal physiology.

neuroscience↗

bioRxiv2019

Regulation of perineuronal nets in the adult cortex by the electrical activity of parvalbumin interneurons

Perineuronal net (PNN) accumulation around parvalbumin-expressing (PV) inhibitory interneurons marks the closure of critical periods of high plasticity, whereas PNN removal reinstates juvenile plasticity in the adult cortex. Using targeted chemogenetic in vivo approaches in the adult mouse visual cortex, we found that transient electrical silencing of PV interneurons, directly or through inhibition of local excitatory neurons, induced PNN regression. Conversely, excitation of either neuron types did not reduce the PNN. We also observed that chemogenetically inhibited PV interneurons exhibited reduced PNN compared to their untransduced neighbors, and confirmed that single PV interneurons express multiple genes enabling cell-autonomous control of their own PNN density. Our results indicate that PNNs are dynamically regulated in the adult by PV neurons acting as sensors of their local microcircuit activities. PNN regulation provides individual PV neurons with an activity-dependent mechanism to control the local remodeling of adult cortical circuits.

neuroscience↗