Dorsomedial striatal dopamine ramps down during interval timing

Dopamine is involved in disorders that degrade cognition such as Parkinsons disease, ADHD, addiction, and schizophrenia; however, it is unclear how dopamine modulates brain circuits involved in cognitive processing. We investigated this problem by recording dopamine during interval timing, an elementary task that requires executive functions to estimate an interval of several seconds by making a motor response. We harnessed the fluorescent dopamine sensor dLight1.3b to record relative dopamine dynamics in the mouse dorsomedial striatum, which integrates information from cognitive cortical circuits and is required for interval timing. We found that: 1) dopamine activity ramped down during interval timing prior to increasing at reward delivery; 2) dopamine ramping dynamics predicted interval timing behavior; and 3) dopamine ramping dynamics were distinct between male and female mice and affected by amphetamine, a potent modulator of dopamine. These data provide insight into how dopamine modulates striatal circuits during interval timing and help better understand how dopamine dynamics contribute to cognitive dysfunction in dopamine-related brain diseases.