TY - JOUR A1 - Otomo, Kanako A1 - Perkins, Jessica A1 - Kulkarni, Anand A1 - Stojanovic, Strahinja A1 - Roeper, Jochen A1 - Paladini, Carlos A. T1 - In vivo patch-clamp recordings reveal distinct subthreshold signatures and threshold dynamics of midbrain dopamine neurons T2 - Nature Communications N2 - 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. KW - Cellular neuroscience KW - Membrane potential KW - Neurophysiology Y1 - 2020 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63747 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-637477 SN - 2041-1723 N1 - This work was funded by grants to J.R. (DFG CRC1080, DFG CRC1193, and NIH DA041705) and C.A.P. (NIH MH113341, MH107229). N1 - Open Access funding enabled and organized by Projekt DEAL. VL - 11.2020 IS - 6286 SP - 1 EP - 15 PB - Nature Publishing Group UK CY - [London] ER -