It is well established that homeostatic signaling systems interface with the mechanisms of developmental and learning-related plasticity to achieve stable yet flexible neural function and animal behavior. Experimental evidence from organisms as diverse as Drosophila, mice and humans demonstrates that homeostatic signaling systems stabilize neural function through the modulation of synaptic transmission, ion channel abundance and neurotransmitter receptor trafficking. At a fundamental level, if homeostatic plasticity is compromised, then the nervous system will be less robust to perturbation. As such, it is widely speculated that defective or maladaptive homeostatic plasticity will be relevant to the cause or severity of autism. However, clear molecular or genetic links between autism and homeostatic plasticity have yet to be defined in any organism.
Graeme Davis hypothesizes that impaired presynaptic homeostatic plasticity could contribute to autism by making the developing nervous system vulnerable to perturbations of any origin, including genetic, environmental or immunological stresses. His laboratory has accumulated preliminary evidence (as part of an earlier SFARI Explorer Award project) that supports this hypothesis. Their data demonstrate a strong interaction between the genetics of autism and the genetics of presynaptic homeostatic plasticity, providing clear molecular evidence that alterations in homeostatic plasticity have direct relevance to autism. Furthermore, the high rate of genetic interaction between homeostatic plasticity and autism-linked gene mutations suggests that presynaptic homeostasis could be a common underlying process that is disrupted by loss-of-function mutations in autism-linked genes.