Circuit mechanisms underlying multisensory integration in the superior colliculus

About the project

About the Project A 2027 Crick PhD project with Florencia Iacaruso. Project background and description The convergence of inputs from different sensory modalities onto individual neurons is a fundamental organisational principle of the nervous system, enabling organisms to integrate complex information about their environment and generate appropriate behavioural responses. This mechanism is conserved across species and occurs throughout the brain. The superior colliculus (SC) is a key hub for multisensory processing, integrating visual, auditory, and somatosensory information to guide orienting behaviours and spatially directed actions. Individual SC neurons respond to multiple sensory modalities, and the interaction between these inputs can generate complex multisensory response properties. While local circuit mechanisms contribute to multisensory processing within the SC, long-range cortical inputs have been proposed to play a critical role in shaping nonlinear multisensory integration. However, the precise organisation of cortical and subcortical inputs onto functionally defined SC neuronal populations remains poorly understood. In particular, it is unknown how the anatomical organisation of inputs relates to the emergence of specific multisensory computations at the level of individual cell types. We hypothesise that distinct functional populations of SC neurons receive specific combinations of cortical and subcortical inputs that generate specialised representations of spatially aligned audiovisual information. Using a custom-built hemispheric stimulation system, spatially coincident visual and auditory stimuli will be presented from multiple locations to probe multisensory responses under controlled behavioural conditions. Combining two- and three-photon calcium imaging will enable the functional mapping of visual, auditory, and multisensory neuronal populations across the SC. To uncover the circuit architecture underlying these functional responses, this project will use Barcoded Rabies In Situ Connectomics (BRISC), a high-throughput approach for mapping neural connectivity across the mouse brain, developed by Petr Znamenskiy’s lab. By combining functional imaging with large-scale connectivity reconstruction, this work will determine layer- and cell-type-specific connectivity rules and identify the long-range cortical and subcortical inputs that target distinct SC neuronal populations. Once we understood the circuitry underlying multisensory integration, we hope to use related approaches to elucidate the circuitry underlying sensorimotor transformations. Together, these approaches will reveal how circuit organisation gives rise to multisensory representations in the SC. By linking functional responses, anatomical connectivity, and genetic identity, this project will establish how specific neuronal populations integrate information from different sensory modalities and may identify molecular markers associated with multisensory processing. Understanding the circuit principles underlying multisensory integration will provide fundamental insight into how the brain combines information from the environment to guide behaviour. Candidate background The successful candidate will either come from a degree in Neuroscience / Molecular Biology with a strong background and interest in mathematics / data science approaches. Alternatively, the successful candidate will come from a degree in Bioengineering, Computational Biology and have a strong background, interest in and enthusiasm for experimental neuroscience / neurophysiology. Extensive quantitative, analytical ability will be essential and experience in computer programming (ideally Python or Matlab) and enthusiasm for advanced data analysis approaches will be highly advantageous. The lab is highly collaborative and ability and enthusiasm to work and communicate in a team is essential. Previous work with animals and experience in in vivo recordings or spatial transcriptomics is desirable but not essential as this can be part of the training programme. Lab-specific question Please describe any experience you have that might help you to interrogate the functional architecture of the brain.

Research areas