Genetics, Molecular Control and Clinical Relevance of Habituation Learning

Abstract

Habituation, the most ancient and fundamental form of learning, manifests already before birth. Neuroscientists have been fascinated for decades by its function as a firewall protecting our brains from sensory information overload and its indispensability for higher cognitive processing. Evidence that habituation learning is affected in autism and related monogenic neurodevelopmental syndromes and their animal models has exponentially grown, but the potential of this convergence to advance both fields is still largely unexploited.In this review, we provide a systematic overview of the genes that to date have been demonstrated to underlie habituation across species. We describe the biological processes they converge on, and highlight core regulatory pathways and repurposable drugs that may alleviate the habituation deficits associated with their dysregulation. We also summarize currently used habituation paradigms and extract the most important arguments from literature that support the crucial role of habituation for cognition in health and disease. We conclude that habituation is a powerful tool to overcome current bottlenecks in research, diagnostics and treatment of neurodevelopmental disorders.

Rapid assessment of the temporal function and phenotypic reversibility of neurodevelopmental disorder risk genes in Caenorhabditis elegans

“…A behavior that has been increasingly used in high-throughput model organisms to investigate the biological function of neurodevelopmental disorder risk genes and functional impact of disorder-associated variants is habituation ( Blok et al, 2022 ; Kepler et al, 2020 ). Habituation is a highly conserved form of non-associative learning observed as a decrement in responding to a repetitive stimulus ( Rankin et al, 2009 ; Thompson and Spencer, 1966 ).…”