Yvonne Maria Johansson

Midbrain dopamine (DA) neurons are crucial for movement, reward, and motivation. In Parkinson’s disease (PD), degeneration of a key DA neuron population results in marked DA loss in the striatum and severe motor impairment. Current treatments aim to replace DA pharmacologically but lack target specificity and temporal control, often delivering excessive, neurotoxic levels that cause severe side effects, precluding further treatment.This project proposes a fundamentally different approach: to characterise a DA population that is spared in PD and to exploit its capacity to restore striatal DA levels. The retrorubral field (RRF) is a neglected midbrain DA nucleus that projects to the striatum, yet remains mostly intact in PD patients, representing an unstudied—and untapped—source of DA in the brain.The goal of this project is to unlock the RRF – to uncover its role in behaviour and to harness its resilience to dynamically restore physiological DA in a PD mouse model using a closed-loop system. We will reveal the roles of RRF cell populations with modern genetic tools, fiber photometry, and behavioural assays, while assessing circuit connectivity and homeostatic adaptations via optogenetics and ex vivo slice electrophysiology.This proposal will fill a critical gap in knowledge of the DA system, provide novel insights into compensatory mechanisms in PD, and aims to develop new circuit-specific therapies that restore endogenous DA to ameliorate motor dysfunction.