Heterogeneity in the Pitx2ON Population in the Mouse Superior Colliculus

The Superior Colliculus (SC) is a conserved midbrain region essential for sensorimotor integration. Pitx2ON neurons, a glutamatergic population in the intermediate SC, are known to drive spatially oriented head movements. These neurons project to various regions, including tecto-spinal systems that govern head and eye movements and the mesocorticolimbic system, hinting at roles beyond motor control. However, it is unclear if the entire Pitx2ON population connects to all identified targets or whether subpopulations with distinct molecular or projection profiles exist. This work investigates heterogeneity within Pitx2ON neurons, starting with single-nucleus RNA sequencing to assess molecular diversity. Differential expression of transcription factors, neurotransmitter receptor genes, and canonical markers suggests a molecularly heterogeneous population. Complementary viral tracing experiments map the connectivity of Pitx2ON neurons. Retrograde tracing from individual downstream targets reveals spatial biases, suggestive of connective heterogeneity within the population. Examination of multiple connectivity suggests partial overlap between motor and thalamus-projecting populations, while no evidence is observed for simultaneous connectivity to thalamic and subthalamic areas. Genetic characterisation of these differentially projecting populations shows that the molecular heterogeneity observed in the single nucleus sequencing data underpins anatomical and potentially functional sub-populations in the Pitx2ON population. Finally, a potential paradigm is discussed for examining the behavioural implications of the thalamus-projecting Pitx2ON neurons. This work reveals molecular and projection heterogeneity in Pitx2ON neurons, suggesting the possibility of distinct subpopulations. These findings contribute to understanding how SC circuits integrate sensory and motor functions and hint at broader roles in cognition.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Williams, Elena

Advisor dc:contributor.advisor

• Tripodi, Marco

• Neuroscience
• Sensory
• Molecular

Licence

• https://www.repository.cam.ac.uk/bitstreams/01702f3c-0611-4944-9bd2-2c2bdef94215/download
• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.117518

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/382936