Fig. 1.

Inhibition of the MGB projection to the auditory striatum impaired animals’ performance in “cloud-of-tones” task. a Left panel, illustration of the projections from the MGB and primary ACx to the auditory striatum. Right panel, Example images of thalamic projections (green) and cortical projection (red) to the auditory striatum. AAV expressing GFP was injected into MGB, and AAV-expressing dTomato was injected into auditory cortex. Images are taken at the auditory striatum. Scale bar, 500 µm. b CNO/DREADD-mediated inhibition of thalamostriatal projection. Left panel, schematic diagram of viral injection and CNO infusion setup. Right upper panel, example image of labeled thalamostriatal fibers. Scale bar: 100 µm. Right lower panel, one example of whole-cell recordings (average EPSCs) on striatal slice showing CNO-mediated terminal inhibition. EPSCs on MSN was elicited by local electrical stimulation on axon fibers, with CNO (10 µM, red) and without CNO (black) application. Bicuculine (20 μM) was added in the bath solution to block local GABAergic activity. Scale bars: 5 pA and 20 ms. c. Left panel, illustration of “cloud-of-tones” task, a two-alternative forced-choice frequency-discrimination task. Right panel, examples of auditory stimuli. d CNO effects on task performance in experimental mice (expressing hM4Di-mCherry, left) and control mice (expressing mCherry only, right). The evidence strength is calculated as (# high tones − # low tones) / (# high tones + # low tones). Error bars are s.e.m. The curve is fitted with logistic sigmoid function. Red: CNO sessions; Black: saline sessions. e–h. Effects of CNO-mediated thalamic inhibition on the slopes of psychometric function (e), the numbers of non-reported trials per session (f), the number of completed trials per session (g), and the reaction time (h). For d–h, n = 5 pairs of sessions from three experimental mice, and three pairs of session from three control mice; error bars are s.e.m., ^*p < 0.05, paired t test