Fig. 2 ∣. Genes and environment affect milestones of brain development in autism.

During human gestation, environmental insults and genetic risk factors can affect typical brain development at specific milestones, eventually leading to the symptoms of autism. These stressors could affect the birth and migration of neurons, their ability to form synaptic connections or generate the earliest forms of spontaneous network activity, and programmed cell death, as well as experience-dependent plasticity and learning. We propose that these changes occur at a critical stage when excitatory and inhibitory neurons participate in a structural and functional handshake (bracket and arrow). By the time symptoms of autism are recognized in toddlers, the circuit alterations may be irreversible, such that a complete restoration of typical network function (even with genetic rescue in single-gene autism disorders) may not be possible. However, it may be feasible to restore circuit function to a more typical regime by interventions after diagnosis. An approximate timeline of the equivalent stages of circuit formation in mice is also shown for comparison.