Exploring the Neural Substrates of Number Sense: A Perspective on Genetics, Behaviour and Neural Circuity.

Number sense is the intuitive, non-verbal ability to perceive and process numerical quantities without formal counting. This evolutionarily conserved trait, shared by different animal species, is supported by two mechanisms: the object tracking system (OTS) for small sets and the approximate number system (ANS) for larger quantities. Although historically viewed as distinct, these systems interact dynamically; their disruption is implicated in developmental dyscalculia and disorders such as Williams-Beuren syndrome (WBS), a chromosome microdeletion characterised by marked numerical and visuospatial deficits. Here, we synthesise neurobiological advances to provide an integrative perspective on the neural substrates of number sense. Field studies provide ecological validity, while laboratory procedures offer tighter precision; together, they illuminate the biological foundations of numerical cognition. Although number sense is conserved, human studies indicate only moderate heritability likely reflecting directional selection. Nonetheless, genetic findings converge on neurodevelopmental and synaptic mechanisms. Zebrafish (Danio rerio) offer a powerful platform to bridge genes, circuits and behaviour. For instance, manipulating zebrafish genes linked to WBS reveals gene-specific effects on quantity processing. At the neural level, numerical cognition is largely supported by specialised number-selective neurons. Whole-brain calcium imaging in larval zebrafish demonstrates that these neurons emerge by 3 days postfertilisation and follow a trajectory where representations of small numerosities precede larger ones. Altogether, integrating genetic, behavioural and circuit-level approaches provides a powerful framework for uncovering conserved mechanisms of numerosity supporting higher-level cognitive functions, including mathematics.