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Research ArticleResearch Article: New Research, Cognition and Behavior

The Serotonin 1B Receptor Modulates Striatal Activity Differentially Based on Behavioral Context

Ka H. Ng, Arati Sharma and Katherine M. Nautiyal
eNeuro 20 January 2026, 13 (2) ENEURO.0413-25.2026; https://doi.org/10.1523/ENEURO.0413-25.2026
Ka H. Ng
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire 03755
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Arati Sharma
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire 03755
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Katherine M. Nautiyal
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire 03755
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    Figure 1.

    Localization of calcium imaging in the DMS. A, Representative photomicrograph showing the location of the GRIN lens track and GCaMP6f expression (green) on a DAPI stained (blue) coronal section. B, Atlas sections show reconstructed localization of the lens placement from each imaged mouse. Blue indicates mice excluded from analysis in the action task, and orange indicates mice excluded from analysis for the waiting task (see Materials and Methods for details).

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    Figure 2.

    DMS calcium activity during an appetitive instrumental task. A, Schematic showing operant trial structure including average percentage of trial types (omission, incorrect, and correct responses) across all mice. B, Behavioral data showing the average number of trials initiated (left) and average latency to respond to the cue on correct trials (right) for controls and mice lacking 5-HT1BRs. C, Heatmaps show the normalized dF/F of all cells averaged over all trials during ITI baselines (left) and correct trials (right) for control (top) and 5-HT1BR KO mice (bottom), sorted by time of peak event rate. D, Normalized event rates are shown averaged for all cells over baseline and trial periods for Control (blue) and 5-HT1BR KO (orange) mice. ***p < 0.0001.

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    Figure 3.

    5-HT1BR influences the balance of excitation and inhibition during goal-directed behavior. A, Traces from example cells showing significant responses during different trial epochs compared with baseline. B, The percentage of cells showing no change (gray), increased (green), or decreased (red) calcium activity during each of four trial epochs (trial initiation, cue presentation, reward presentation, post reward consumption) compared with baseline are shown for control (top) and 5-HT1BR KO (bottom). C, Radial plot shows the percentage of responsive cells according to their mixed selectivity across all four trial epochs for control (orange) and 5-HT1BR KO (blue) mice. T, trial initiation period; C, cue period; R, reward period; P, post reward period; +, significant excitatory response; −, significant inhibitory response; *p < 0.05; #p < 0.07.

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    Figure 4.

    5-HT1BR expression influences DMS activity associated with reward. A, Normalized calcium event rates are plotted for cells showing a significant response to reward for control (top) and 5-HT1BR KO (bottom) mice relative to cue response (yellow dashed line). B, The percentage of responsive cells that are responsive to the reward and post reward epochs, regardless of their responses to trial initiation or cue presentation, are shown for both genotypes. C, The average calcium activity is shown for cells classified as excited during the reward period (R+), post reward period (P+), or both (R + P+), or inhibited during the post reward period (P−) for control (blue) and 5-HT1BR KO (orange) mice. *p < 0.05.

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    Figure 5.

    Mice lacking 5-HT1BRs have more active MSNs during the delay period. A, Schematic showing the two-choice serial reaction time task including average percentage of trial types (omission, incorrect, and correct responses) across all mice including sessions with 3 s and 6 s delays. B, The percentage of responsive cells that show increases in calcium event rates during the trial initiation and/or delay window periods for both genotypes. C, Normalized calcium event rates for cells averaged over all correct trials for Control (top) and 5-HT1BR KO mice (bottom), sorted by time of peak event rate. D, Percentage of D+ cells for each mouse plotted against impulsive behavior measured by percentage of premature trials within the imaging session. T+, cells significantly excited during the trial initiation period; D+, cells significantly excited during the delay period; T + D+, cells that are significantly excited during both trial initiation and delay period. ***p < 0.001.

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    Figure 6.

    Training increases amplitude, but not proportion of delay window response neurons. A, Behavioral performance is shown as the percentage of trials with premature responses during the delay window. B, The percentage of responsive cells that show increases in calcium event rates during the trial initiation and/or delay window periods for both genotypes in the first and sixth training sessions of the waiting task. C, Normalized calcium event rates for cells showing significant increases in calcium activity during the delay period, averaged over all correct trials for the first (darker) and sixth (lighter) sessions. D, Scatterplots show correlations of the amplitude of the z normalized calcium event rate for individual cells showing increases in calcium activity during the delay period as a function of the number of impulsive responses made during the delay period for the first (left) and sixth (right) sessions. Lines of best fit are plotted for cells from mice from each genotype separately. *p < 0.05; **p < 0.001.

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The Serotonin 1B Receptor Modulates Striatal Activity Differentially Based on Behavioral Context
Ka H. Ng, Arati Sharma, Katherine M. Nautiyal
eNeuro 20 January 2026, 13 (2) ENEURO.0413-25.2026; DOI: 10.1523/ENEURO.0413-25.2026

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The Serotonin 1B Receptor Modulates Striatal Activity Differentially Based on Behavioral Context
Ka H. Ng, Arati Sharma, Katherine M. Nautiyal
eNeuro 20 January 2026, 13 (2) ENEURO.0413-25.2026; DOI: 10.1523/ENEURO.0413-25.2026
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Keywords

  • 5-HT1BR
  • action
  • dorsomedial striatum
  • inhibition
  • reward
  • serotonin

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