Spontaneous Neurotransmitter Release Shapes Dendritic Arbors via Long-Range Activation of NMDA Receptors

•New role for spontaneous neurotransmitter release in dendritic arbor formation•Vesicular glutamate can activate distant “long-range” dendritic NMDA receptors•Presynaptic and postsynaptic machinery operate before synaptic contact•Spontaneous glutamate release may provide local dendritic guidance or branching cue

SummarySpontaneous neurotransmitter release is a core element of synaptic communication in mature neurons, but despite exceptionally high levels of spontaneous vesicle cycling occurring in developing axons, little is known of its function during this period. We now show that high-level, spontaneous axonal release of the neurotransmitter glutamate can signal at long range to NMDA receptors on developing dendrites, prior to synapse formation and, indeed, axodendritic contact. Blockade of NMDA signaling during this early period of spontaneous vesicle cycling leads to a reduction in dendritic arbor complexity, indicating an important role for early spontaneous release in dendritic arbor growth.

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