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Healthy DA SN neurons show diverse firing patterns in vivo, ranging from slow pacemaker-like activity (1\u201310 Hz) to transient high-frequency bursts (&lt;100 Hz), interspersed with pauses that can last hundreds of milliseconds. Recent in vivo patch experiments have started to reveal the subthreshold mechanisms underlying this physiological diversity, but the impact of challenges like cell loss on the in vivo activity of adult DA SN neurons, and how these may relate to behavioral disturbances, is still largely unknown. We investigated the in vivo electrophysiological properties of surviving SN DA neurons after partial unilateral 6-OHDA lesions, a single-hit, non-progressive model of neuronal cell loss. We show that mice subjected to this model have an initial motor impairment, measured by asymmetrical rotations in the open field test, which recovered over time. At 3 weeks post-lesion, when open field locomotion was strongly impaired, surviving DA SN neurons showed a compressed in vivo dynamic firing range, characterized by a 10-fold reduction of in vivo burst firing compared to controls. This in vivo phenotype was accompanied by pronounced in vitro pacemaker instability. In contrast, in the chronic post-lesion phase (&gt;2 months), where turning symmetry in open field locomotion had recovered, surviving SN DA neurons displayed the full dynamic range of in vivo firing, including in vivo bursting, similar to controls. The normalized in vivo firing pattern was associated with a twofold acceleration of stable in vitro pacemaking, mediated by Kv4.3 potassium channel downregulation. Our findings demonstrate the existence of a homeostatic pacemaker plasticity mechanism in surviving DA SN neurons after pronounced cell loss.<\/jats:p>","DOI":"10.7554\/elife.104037","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T09:15:07Z","timestamp":1757495707000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.104037","source":"Crossref","is-referenced-by-count":3,"title":["Recovery of the full in vivo firing range in post-lesion surviving DA SN neurons associated with Kv4.3-mediated pacemaker plasticity"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6999-1533","authenticated-orcid":true,"given":"Lora","family":"Kovacheva","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cvxnb49","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Neurophysiology, Neuroscience Center, Goethe University Frankfurt","place":["Frankfurt, 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