Locomotion-dependent auditory gating to the parietal cortex guides multisensory decisions

Article https://doi.org/10.1038/s41467-025-57347-y Locomotion-dependent auditory gating to the parietal cortex guides multisensory decisions Received: 5 March 2024 Ilsong Choi1 & Seung-Hee Lee 1,2 Check for updates 1234567890():,; 1234567890():,; Accepted: 13 February 2025 Decision-making in mammals fundamentally relies on integrating multiple sensory inputs, with conflicting information resolved flexibly based on a dominant sensory modality. However, the neural mechanisms underlying state-dependent changes in sensory dominance remain poorly understood. Our study demonstrates that locomotion in mice shifts auditory-dominant decisions toward visual dominance during audiovisual conflicts. Using circuitspecific calcium imaging and optogenetic manipulations, we found that weakened visual representation in the posterior parietal cortex (PPC) leads to auditory-dominant decisions in stationary mice. Prolonged locomotion, however, promotes visual dominance by inhibiting auditory cortical neurons projecting to the PPC (ACPPC). This shift is mediated by secondary motor cortical neurons projecting to the auditory cortex (M2AC), which specifically inhibit ACPPC neurons without affecting auditory cortical projections to the striatum (ACSTR). Our findings reveal the neural circuit mechanisms underlying auditory gating to the association cortex depending on locomotion states, providing insights into the state-dependent changes in sensory dominance during multisensory decision-making. Multisensory integration in the brain, which combines neural information from different sensory modalities, is essential for goal-directed perceptual decisions in an ever-changing environment1. Animals can make faster2,3 and more accurate4,5 perceptual decisions when they integrate congruent (coherent) multisensory stimuli. On the other hand, animals frequently prioritize one modality over the other in response to conflicting multisensory stimuli and show sensory dominance in their perceptual decisions6–13. For instance, when head-fixed mice faced conflicting audiovisual cues (one instructed ‘Go’ responses while the other instructed ‘No-go’ responses), they often made decisions following auditory cues12,13. This sensory dominance in multisensory decisions cannot be fully explained by a simple additive integration of individual stimuli as explained by a classic Bayesian model14–16. Rather, it requires under-weighting one modality more than the other before the integration10,11,17, potentially via cross-modal inhibition12,18,19. Interestingly, the prepotent modality in multisensory decisions not only varies individually but also switches flexibly from trial to trial10,11,20,21. Neural underpinnings of such changes in sensory dominance, however, remain largely unexplored. Perceptual decision-making occurs with sensory representation associated with motor actions across cortical areas22,23. The sensory representation is not stable and fluctuates depending on the behavioral states of the animals24,25. One key factor affecting the cortical representation of sensory stimuli is the locomotion. Locomotion increases arousal, which amplifies visual gain in the visual cortex (VC)26–34 but suppresses auditory representations in the auditory cortex (AC)35,36. Furthermore, locomotion generates corollary discharge signals copied from motor commands, which also suppress auditory responses in the AC37,38. As a result of these representational changes, mice showed better detection of mild visual cues27 and reduced detection of weak auditory cues35,39. Despite this, animals still can identify salient auditory cues well and perform auditory-dependent 1 Center for Synaptic Brain Dysfunctions, IBS, Daejeon 34141, Republic of Korea. 2Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea. e-mail: Nature Communications | (2025)16:2308 1 Article https://doi.org/10.1038/s41467-025-57347-y perceptual tasks without disruption even during locomotion40,41. These reports suggest that, even during locomotion, animals retain salient auditory information in the brain, enabling them to make appropriate auditory decisions. In a multisensory environment containing both visual and auditory stimuli, it is more challenging to determine how locomotion influences the multisensory representation and decisionmaking processes. Compared to head-fixed mice, freely roaming mice exhibited no differences in unisensory decisions but only shifted prepotent modality from audition to vision during multisensory decisions13. However, it is unclear how locomotion modulates neural circuits representing multisensory stimuli in the brain to alter behavioral decisions in mice. One of the key brain areas that mediate perceptual decisionmaking is the posterior parietal cortex (PPC)42–44. The PPC encodes various task-relevant activities during visual decision-making tasks. For example, the PPC conveys visual information45–48, accumulating sensory evidence49,50, history of the task variables47,51, animal’s choices45,47,52–54, and body movements55. Furthermore, inactivation of the PPC resulted in a substantial decline in an animal’s ability to make visual decisions45,53,56. Similar to the visual activities, the PPC also showed task-relevant activities during auditory decision-making tasks47,56–59. Its inactivation, however, did not impair perceptual decisions based on simple auditory cues, such as feature detection or discrimination in well-trained animals48,56,60. Instead, PPC activity was required for more complex auditory-dependent decision-making, which involves higher levels of cognitive processing58,61,62. The PPC receives converging inputs from visual, auditory, and somatosensory cortices63–65 and responds to multisensory stimuli in humans66, primates19,67 and rodents68,69. However, its role in multisensory decisions is still unclear. PPC inactivation altered multisensory decisions under audiovisual conflicts12 (but see also16), but it did not affect multisensory decisions in coherent conditions16,56. These reports suggest that the PPC in multisensory decisions may depend on the task paradigms or multisensory contexts that the animal encounters. To understand how the PPC is involved in multisensory decisions in animals making perceptual decisions across auditory, visual, and congruent or incongruent audiovisual stimuli, at different behavioral states, we used in vivo calcium imaging and optogenetic manipulation techniques in mice performing an audiovisual discrimination task on a treadmill. We discovered that the dominant modality can be switched from audition to vision during locomotion. The PPC neurons discriminated visual inputs better than auditory inputs, and the visual representation was suppressed when animals made auditorydominant decisions in audiovisual conflicts. During locomotion, the AC output to the PPC (ACPPC) was selectively suppressed, while the AC output to the striatum (ACSTR) was maintained. This circuit-specific modula (...truncated)