In vivo patch-clamp recordings reveal distinct subthreshold signatures and threshold dynamics of midbrain dopamine neurons

  • The in vivo firing patterns of ventral midbrain dopamine neurons are controlled by afferent and intrinsic activity to generate sensory cue and prediction error signals that are essential for reward-based learning. Given the absence of in vivo intracellular recordings during the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. To address this, we established in vivo whole-cell recordings and obtained over 100 spontaneously active, immunocytochemically-defined midbrain dopamine neurons in isoflurane-anaesthetized adult mice. We identified a repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. Dopamine neuron activity in vivo deviated from single-spike pacemaking by phasic increases in firing rate via two qualitatively distinct biophysical mechanisms: 1) a prolonged hyperpolarization preceding rebound bursts, accompanied by a hyperpolarizing shift in action potential threshold; and 2) a transient depolarization leading to high-frequency plateau bursts, associated with a depolarizing shift in action potential threshold. Our findings define a mechanistic framework for the biophysical implementation of dopamine neuron firing patterns in the intact brain.
Author:Kanako OtomoORCiDGND, Jessica Perkins, Anand Kulkarni, Strahinja StojanovicORCiD, Jochen RoeperORCiD, Carlos A. PaladiniORCiD
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Date of Publication (online):2020/12/08
Date of first Publication:2020/12/08
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2022/10/27
Tag:Cellular neuroscience; Membrane potential; Neurophysiology
Article Number:6286
Page Number:15
First Page:1
Last Page:15
This work was funded by grants to J.R. (DFG CRC1080, DFG CRC1193, and NIH DA041705) and C.A.P. (NIH MH113341, MH107229).
Open Access funding enabled and organized by Projekt DEAL.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0