A Developmental Switch for Hebbian Plasticity.

Hebbian forms of synaptic plasticity are required for the orderly development of sensory circuits in the brain and are powerful modulators of learning and memory in adulthood. During development, emergence of Hebbian plasticity leads to formation of functional circuits. By modeling the dynamics of neurotransmitter release during early postnatal cortical development we show that a developmentally regulated switch in vesicle exocytosis mode triggers associative (i.e. Hebbian) plasticity. Early in development spontaneous vesicle exocytosis (SVE), often considered as 'synaptic noise', is important for homogenization of synaptic weights and maintenance of synaptic weights in the appropriate dynamic range. Our results demonstrate that SVE has a permissive, whereas subsequent evoked vesicle exocytosis (EVE) has an instructive role in the expression of Hebbian plasticity. A timed onset for Hebbian plasticity can be achieved by switching from SVE to EVE and the balance between SVE and EVE can control the effective rate of Hebbian plasticity. We further show that this developmental switch in neurotransmitter release mode enables maturation of spike-timing dependent plasticity. A mis-timed or inadequate SVE to EVE switch may lead to malformation of brain networks thereby contributing to the etiology of neurodevelopmental disorders.