Abstract
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.
Highlights
Functional circuits in the brain are rapidly established during early development and are finetuned by experience throughout life
During early neuronal development this machinery matures such that neurotransmitter release becomes time-locked to action potentials
We studied the effect of the three primary modes of vesicular exocytosis (SVE, aEVE and sEVE) on synaptic competition between synapses using a vesicle-timing dependent plasticity model, where presynaptic neurotransmitter release correlated with postsynaptic activity was necessary for Hebbian plasticity
Summary
Functional circuits in the brain are rapidly established during early development and are finetuned by experience throughout life. For example, cortical columns form in the first three weeks after birth [1,2] During this period, thalamo-cortical input is essential for columnar formation [3] and stimulus-evoked activity patterns further refine cortical connectivity [4]. Activity-dependent forms of synaptic plasticity, in particular Hebbian plasticity, guide the cortical refinement and are required for functional maturation of cortical circuits [5]. Synapses are established, but functional communication between neurons is lacking During this initial phase, spontaneous vesicle exocytosis can help to maintain synapses [9,10]. We propose that a switch in vesicular exocytosis mode ensures a discrete onset for Hebbian plasticity and triggers the activity-dependent neural circuit formation during neurodevelopment
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