Laetitia Etchepare, Laurent Groc et al in the Journal of Physiology

Abstract

Midbrain dopaminergic (DA) neurons play a central role in major physiological brain functions, and their dysfunctions have been associated with neuropsychiatric diseases. The activity of midbrain DA neurons is controlled by ion channels and neurotransmitter receptors, such as the glutamate NMDA receptor (NMDAR) and small-conductance calcium-dependent potassium(SK) channels. However, the cellular mechanisms through which these channels tune the firing pattern of mid brain DA neurons remain unclear. Here, we investigated whether the surface dynamics and distribution of NMDARs tunes the firing pattern of midbrain DA neurons. Using a combination of single molecule imaging and electrophysiological recordings, we report that NMDARs are highly diffusive at the surface of cultured midbrain DA neurons from rodents and humans. Reducing acutely the NMDAR membrane dynamics, which leaves the ionotropic function of the receptor intact, robustly altered the firing pattern of midbrain DA neurons without altering synaptic glutamatergic transmission. The reduction of NMDAR surface dynamics reduced apamin (SK channel blocker)-induced firing change and the distribution of SK3 channels in DA neurons. Together, these data show that the surface dynamics of NMDAR, and not solely its ionotropic function, tune the firing pattern of midbrain DA neurons partly through a functional interplay with SK channel function.

Hightlight

This article is highlighted in a Perspectives article by Susan Jones (University of Cambridge)

De-mobilisation of NMDA receptors in midbrain dopamine neurons: a quantum of reward (PDF)

 

First Author

Laetitia Etchepare
she was a researcher at the Interdisciplinary Institute of Neurosciences in Bordeaux (France). With a training in cell biology and neurosciences, she graduated from the University of Bordeaux in 2018.
Her research focused on the understanding of dopamine neuron physiology and the molecular mechanism underpinning the various firing patterns of these neurons.

Corresponding author

Laurent Groc
Team leader – IINS

Reference

NMDA receptor membrane dynamics tunes the firingpattern of midbrain dopaminergic neurons
Laetitia Etchepare, Hélène Gréa, Pauline Durand, Delphine Bouchet and Laurent Groc
Journal of Physiology ; 02 March 2021
https://doi.org/10.1113/JP281104.