Extracellular spike waveform analysis reveals cell type-specific changes in the superior colliculus of fragile X mice

Abstract

A long-standing goal of neuroscience has been to elucidate the diverse complement of neurons in the brain, which can be defined by several criteria. Analysis of action potential shape in extracellular recordings has revealed subpopulations in several regions of the brain, allowing for insights into neuronal subtype-specific function in the intact brain. The superior colliculus (SC) is a critical sensorimotor region, integrating visual, somatosensory, auditory, and nociceptive inputs to direct complex behaviors. Recent work suggests that the SC may be adversely impacted in neurodevelopmental disorders (NDDs), underscoring its importance. However, our understanding of cellular diversity in the SC lags in comparison to other regions, limiting our ability to parse circuit changes in NDDs. Here, we utilized semi-automated clustering methods to classify neurons in the mouse SC based on multiple features of extracellularly recorded waveforms to identify five putative cell types. Secondary analysis of firing statistics and visual tuning properties supported the cluster segregation. Interestingly, the proportions of units assigned to each cluster differed in the SC of a mouse model of fragile X syndrome (FXS, Fmr1-/y), with only four of five types identified. Furthermore, we observed changes in waveform properties and firing statistics, but not visual tuning properties, between genotypes in a subtype-specific manner. Taken together, these data add to our understanding of neuronal diversity in the SC and alterations of visual circuit organization and function in NDDs.