Kavli Affiliate: Darcy Peterka
| Authors: Eddy Albarran, Akira Fushiki, Anders Nelson, David Ng, Corryn Chaimowitz, Laudan Nikoobakht, Tanya Sippy, Darcy S Peterka and Rui M Costa
| Summary:
The basal ganglia and midbrain dopaminergic systems are critical for motor control, reward processing, and reinforcement learning, with dysfunction in these systems implicated in numerous neurodegenerative and neuropsychiatric disorders. To enable precise genetic targeting of key neuronal populations, we generated and characterized five knock-in mouse lines: Drd1-Cre, Adora2a-Cre, Drd1-FlpO, Adora2a-FlpO, and DAT-FlpO. These lines allow for Cre-or FlpO-mediated recombination in dopamine D1 receptor-expressing spiny projection neurons (SPNs), adenosine A2a receptor-expressing SPNs, and dopamine transporter (DAT)-expressing neurons in the midbrain. Histological analyses confirmed recombinase activity in expected brain regions, and whole-cell electrophysiological recordings validated the intrinsic excitability profiles of each neuronal subpopulation. These tools provide high specificity and reliability for studying basal ganglia circuitry and dopaminergic neurons. By enabling targeted manipulations, these openly available knock-in lines will advance research into the neural mechanisms underlying motor control, reward, and neuropsychiatric diseases.