<EM>IN VIVO</EM> ASSESSMENT OF D1/D2 NEURONAL ACTIVITY IN CORTICO-STRIATAL LOOPS IN <EM>PRG1</EM>-DEFICIENT MICE

Plasticity-related gene 1 (PRG1) is a brain-specific membrane protein located at glutamatergic synapses, where it modulates lysophosphatidic acid (LPA)-dependent signaling and regulates excitatory transmission. PRG1 deletion increases presynaptic glutamate release probability and promotes network hyperexcitability, but its impact on motor control via cortico-striatal circuits and dopamine receptor-specific striatal neuron populations is still unknown. Here, we investigate how conditional Prg1 loss in D1- versus D2-expressing neurons affects neuronal activity along the M1–dorsolateral striatum axis in head-fixed, awake & behaving mice. We conducted silicon probe (Neuropixels 1) recordings spanning primary motor cortex (M1) and dorsolateral striatum (dlS) in two lines, Prg1^fl/fl × D1-Cre and Prg1^fl/fl × D2-Cre, and relate single-unit and population firing to spontaneous movements. Ongoing analyses focus on pathway-specific changes in firing rates, temporal coupling to movement onset and offset, and the coordination of cortical and striatal activity across the two conditional lines. Preliminary observations indicate line-dependent differences in striatal activity patterns and their relationship to motor output, suggesting that PRG1 in D1- versus D2-pathways differentially shapes cortico-striatal dynamics. These data will help to understand how motor adaptation via lipid signaling shapes the balance between direct and indirect pathways regulating motor control and motor flexibility.