Mouse behavior and neural activities of dopamine and D1- and D2- neurons in the tail of the striatum under threat-reward conflict and dopamine action onto the striatal neurons

We recorded dopamine sensor signals and calcium indicator signals in dopamine receptor type 1-expressing neurons (D1-neurons) and dopamine receptor type 1-expressing neurons (D2 neurons) in the tail of the striatum (TS), while thirsty mice collected water in the presence of a big moving object (“monster paradigm”). In some experiments, we examined mouse behaviors in the monster paradigm with manipulation of TS (and dorsolateral striatum, DLS as comparison) such as ablation of TS-projecting dopamine neurons, or D1 neurons or D2 neurons in TS, increase of dopamine concentration in TS, and blocking or activating dopamine receptor type 1 (D1R) or D2R. To map dopamine responses to sensory stimuli and reward in the striatum, we recorded dopamine sensor signals in the various parts of the striatum while mice were presented with reward or tone in head-fixed mice (“tone-reward paradigm”). In addition, we performed optogenetic activation of dopamine axons in TS in head-fixed preparation and examined its effects on sensory responses of D1-neurons and D2 neurons (“optogenetic activation of TS dopamine”).

Methods
GRABDA2m or GRABDA3m was expressed in the striatum to record dopamine. GCaMP7f or GCaMP8m was expressed in the striatum in Tac1- or Adora2A-cre mice to record activity of D1- or D2-neurons. An optic fiber was implanted at a recording location to measure population activity (fiber fluorometry or photometry). Recordings were performed either in a monster paradigm where thirsty mice collected water in a foraging arena with or without a monster object, a tone-reward paradigm where head-fixed mice were presented different sizes of water or tone, or in optogenetic experiments where mice were presented with a sensory stimulus with or without optogenetic activation of dopamine axons in the tail of the striatum.

Dopamine, D1-, or D2-neuron ablation or drug infusion was performed and animal behavior was tested in a monster paradigm with or without a big moving, big static, medium moving, or small moving monster.

In the monster paradigm, mice were first trained to obtain a water reward (10 mL) located in the foraging arena (40 cm from the door) without monster for 3 days. Mice were first placed in a shelter and allowed to forage in a foraging arena. Door was closed after the mouse returned to the shelter and 20 sec ITI was given. After training, test sessions with or without a monster were given. In the monster sessions, when the mouse crossed an invisible trigger line (30 cm from the door), a monster started to move toward door (10 cm, 20 cm/s) and stayed for 500 ms during which a loud sound was presented, then the monster moved backward. This sequence was continued until the mouse returned to the shelter. 10 trials for 1 session.