Functional Nano-segregation of Distinct Forms of Neurotransmission.

Within the single micron of the synapse, three distinct modes of neurotransmission, driven by synchronous, asynchronous, and spontaneous neurotransmitter release, occur concurrently. In this chapter, we discuss the synaptic nano-organization comprised of neurotransmitter release machinery, molecular platforms, scaffolding proteins, and liquid complexes that support the discrete signaling of these three modes of neurotransmission. This robust nano-organization supports unique functional roles for each discrete mode at both excitatory glutamatergic and inhibitory GABAergic synapses. Modular nanocolumn organization of excitatory synapses and largely single-domain organization of inhibitory synapses maintain homeostatic plasticity within neural circuits. These recent findings support a basic design principle where the single synapse is a highly ordered and compartmentalized unit that by the functional nano-segregation of distinct forms of neurotransmission shapes synaptic efficacy, determines neurotransmission reliability, and tunes plasticity. The development of novel tools will be instrumental in further elucidating the nano-environment of the synapse, essential to both uncovering mechanisms underlying neurological disorders as well as their treatment.