Activation of Striatal Neurons Causes a Perceptual Decision Bias during Visual Change Detection in Mice

Abstract

The basal ganglia are implicated in perceptual decision-making, although their specific contributions remain unclear. Here, we tested the causal role of the basal ganglia by manipulating neuronal activity in the dorsal striatum of mice performing a visual orientation-change detection (yes/no) task. Brief unilateral optogenetic stimulation caused large changes in task performance, shifting psychometric curves upward by increasing the probability of "yes" responses with only minor changes in sensitivity. For the direct pathway, these effects were significantly larger when the visual event was expected in the contralateral visual field, demonstrating a lateralized bias in responding to sensory inputs rather than a generalized increase in action initiation. For both direct and indirect pathways, the effects were specific to task epochs in which choice-relevant visual stimuli were present. These results indicate that the causal link between striatal activity and decision-making includes an additive perceptual bias in favor of expected or valued visual events.

Keywords: basal ganglia; detection; mice; mouse; perception; striatum; visual.

Figure 1. Visual orientation-change detection task and examples of behavioral performance

(A) Localization of optogenetic stimulation in striatum. Left: stereotaxic placement of fiber and optogenetic stimulation. Right: coronal section from example Drd1a-cre mouse, showing viral expression in dorsomedial striatum and placement of optical fiber. (B) Top-down view of the behavioral apparatus, showing a head-fixed mouse on the polystyrene wheel viewing left and right visual displays. (C) Sequence of visual epochs during the task, illustrating a trial during left change blocks. The length of each epoch was measured by the distance traveled on the wheel. (D–E) Timeline of events during change (D) and no-change trials (E) interleaved in the block. The outcome of a trial was determined by whether the first lick fell within the 500ms response window starting 300 ms after the stimulus change. The 150ms optogenetic stimulation ended before the onset of the response window. (F–I) Cumulative lick probabilities from an example session in one Drd1a-cre mouse, divided to illustrate the 8 possible trial types. A 12° orientation change was used in this session, and only the timing of the first lick made by the mouse on each trial was used for quantification, aligned to the onset of the change epoch. Data are from the same mouse as shown in panel A (right).

Figure 2. Optogenetic activation of the direct pathway increased response bias preferentially for visual events on the contralateral side

(A) Sagittal section of an example Drd1a mouse, showing Cre-dependent viral expression in the striatum and downstream axonal targets of transfected neurons (GPi, SNr and GPe). Scale bar,1mm. Yellow: YFP, magenta: anti-GFP/YFP antibody staining. (B) Summary of unilateral optic fiber tip placements in the striatum of all the Drd1a-cre used in the study (grey dots). The number label indicates the tip placement for the example mouse whose data are shown in C. (C) Psychometric data of an example Drd1a-cre mice. Circles show lick probability pooled across sessions for each orientation change tested. Smooth curves show fitted cumulative Gaussian function. Error bars show 95% confidence interval. Left: psychometric data for orientation change contralateral to the optic fiber implant, with (orange) and without (brown) optical stimulation. Right: psychometric data for orientation change ipsilateral to the optic fiber implant, with (light blue) and without (dark blue) optical stimulation. (D) Fitted psychometric curves from all Drd1a mice (n=9); each curve is from one mouse. Left: psychometric curves for performance during blocks containing contralateral visual events, with (orange) and without (brown) stimulation. Right: psychometric curves during blocks with ipsilateral visual events, with (light blue) and without (dark blue) stimulation. (E) Comparison of response biases from psychometric curves with and without dMSN stimulation, during blocks containing contralateral (orange) and ipsilateral (blue) visual events. Filled circles are data from each mouse, open circles represent population average. Error bars are 95% CI. (F) Comparison of JNDs from psychometric curves with and without dMSN stimulation. See also Figure S1.

Figure 3. Optogenetic activation of the indirect pathway increased response bias equally for visual events in either visual hemifield

(A) Sagittal section of an example A2a mouse, showing Cre-dependent viral expression in the striatum and downstream axonal targets of transfected neurons (GPe only). Scale bar,1mm. Yellow: YFP, magenta: anti-GFP/YFP antibody staining. (B) Summary of unilateral optic fiber tip placements for all A2a-cre mice used in the study (grey dots). Number label indicates the tip placement for the example mouse whose data are shown in C. (C) Psychometric data of an example A2a-cre mice. (D) Fitted psychometric curves from all A2a-cre mice (n=10). (E) Comparison of response biases from psychometric curves with and without iMSN stimulation. (F) Comparison of JNDs from psychometric curves with and without iMSN stimulation. Other conventions same as in Figure 2.

Figure 4. Optical stimulation in YFP control mice did not change psychophysical performance

(A) Population summary of psychometric curves with and without optical stimulation from all 8 mice injected with eYFP virus. (B) Comparison of response biases from psychometric curves with and without optical stimulation. (C) Comparison of JNDs from psychometric curves with and without optical stimulation. Other conventions same as in Figure 2.

Figure 5. Summary of psychophysical performance with and without striatal optogenetic stimulation

(A) Comparison of striatal stimulation effects on response bias in Drd1a-cre, A2a-cre and YFP mice, defined as response bias with stimulation minus response bias without stimulation. (B) Comparison of striatal stimulation effects on JND in all three genotypes, defined as JND with stimulation minus JND without stimulation. (C) Mean psychometric curves obtained by pooling data across all 9 Drd1a mice, separately for contralateral and ipsilateral blocks, and with and without striatal stimulation. (D) Mean psychometric curves from all 10 A2a mice. (E) Chronometric curves of response latency for contralateral visual changes with and without striatal stimulation, pooled across all Drd1a mice. (F) Chronometric curves of response latency for contralateral visual changes, pooled across all A2a mice. (G) Chronometric curves for ipsilateral visual changes from Drd1a mice. (H) Chronometric curves for ipsilateral visual changes from A2a mice. Error bars are median ± 95% CI. ***p<0.001, **p<0.01, *p<0.05. See also Figures S2-S5.

Figure 6. Effects of striatal stimulation on response criterion and latency emerged after a few trials within a block

(A) Effects on response criterion caused by dMSN stimulation plotted as a function of trial number during a block. Change in criterion (defined as stimulation minus no stimulation) shown separately for blocks containing contralateral (orange) or ipsilateral (blue) 12° orientation chan ges. Each open circle shows the population median (n=11) of the induced changes for that trial number in the block. Error bar: SEM. The symbol (*) indicates a significant difference (p<0.05, Wilcoxon rank sum test) between contralateral and ipsilateral values. (B) Time course of changes in response criterion caused by iMSN stimulation. (C–D) Time course of changes in response latency caused by dMSN (C) or iMSN (D) stimulation.

Figure 7. Changes in performance caused by striatal stimulation depended on the presence of behaviorally relevant visual stimuli

(A) Schematics of visual displays and timing of optogenetic stimulation in sequence-arrested control trials and normal no-change (‘two-patch’) trials. All sequence-arrested control trials had optical stimulation at a distance equivalent to normal trials, and were interleaved with 12° cha nge and no-change trials. (B) Lick probability during response window observed across different conditions in Drd1a-cre mice when visual event could occur in contralateral (orange) and ipsilateral (blue) hemifield. Filled circles represent data from individual mice, open circles show population mean. Error bars are 95% CI. (C) Lick probability during response window observed across different conditions in A2a-cre mice.

Figure 8. Lick-related Ca²⁺ transients in dMSNs occurred only when behaviorally relevant visual stimuli were present

(A) Diagram of fiber photometry setup to record population GCaMP6f signals in striatal dMSNs. (B) ΔF/F traces of GCaMP6f signals (green, 465nm) and autofluorescence (grey, 405nm) from an example trial containing a hit response. Vertical lines (grey) indicate onset of each epoch and the onset of the first lick (purple). (C) Time course of normalized population mean (n=8) GCaMP6f signals aligned to lick onset during different epochs when visual event could occur in contralateral (orange) or ipsilateral (blue) hemifield. Thick lines represent mean and shading indicates SEM. Light green stripes in left panel indicate 100ms time windows used to calculate the amplitude of GCaMP6f transients in panel D, purple arrow indicates time of mean onset of lick-related GCaMP6f transients (−161 ms). (D) Amplitude of lick-related GCaMP6f transient during different visual epochs. Each filled circle shows data from one mouse, open circles are population mean, and error bars indicate SEM. See also Figure S6.