Fig. 5: LHb input to MRN drives disengagement.

a, Retrograde tracing from MRN using retroAAV (left), and image of retrogradely labelled neurons in LHb (right). Scale bar, 0.25 mm. b, Schematic of optogenetic activation or suppression of LHb input to MRN (left), and image of ChR2-expressing LHb axons in the MRN with optic fibre positions (right). Scale bar, 0.5 mm. c, Schematic of the self-stimulation test (left), and preference for returning to the opto-linked nose-poke port (calculated as in Fig. 4e) in control mice compared with mice with suppression or activation of LHb input to the MRN (right; n = 9, 5 and 9 mice, respectively). d,e, Median fraction of time spent in the three interaction states during the MNOI test in mice with activation (d, left) and suppression (d, right) of LHb input to the MRN and in control mice (e). n = 20, 20 and 15 experiments from 10, 9 and 5 mice in control, activation and suppression groups, respectively. f, Schematic of nose-poke reward association task with activation of LHb input to the MRN (left) and examples of task performance (including timing of nose pokes, licks and completed (compl.) trials) of a control mouse and a mouse with activation of LHb input to the MRN. Light blue boxes indicate laser stimulation periods. Right, average number of completed trials during laser stimulation in tdTomato mice and mice with activation of LHb input in the MRN (n = 14 and 10 mice, respectively). g, Experimental design for recording calcium signals in MRN cell types using fibre photometry, while optogenetically activating LHb input to the MRN. h, z-Scored calcium traces (mean ± s.e.m.) aligned to laser onset, showing the effect of optogenetic activation of LHb input on the activity of VGAT⁺ (left; n = 4 mice), VGluT2⁺ (middle; n = 5 mice) and SERT+ (right; n = 4 mice) neurons in MRN. i, Top, schematic of experimental design to obtain calcium recordings from SERT⁺ MRN neurons, while activating LHb input to the MRN during the first deep interaction with objects. Bottom, z-scored calcium activity (mean ± s.e.m.) aligned to onset of first deep object interaction with and without optogenetic activation of LHb input to the MRN. n = 10 (laser off) versus 7 (laser on) events from 3 mice. ***P < 0.001. In c,e,f, bars indicate median values, error bars are bootstrapped standard error and circles represent individual experimental sessions. See Extended Data Table 1 for statistics.

Source data