Synapses are highly specialized neuronal structures that are essential for neurotransmission, and they are dynamically regulated throughout the lifetime. Although accumulating evidence indicates that these structures are crucial for information processing and storage in the brain, their precise roles beyond neurotransmission are yet to be fully appreciated. Genetically encoded fluorescent tools have deepened our understanding of synaptic structure and function, but developing an ideal methodology to selectively visualize, label and manipulate synapses remains challenging. Here, we provide an overview of currently available synapse labelling techniques and describe their extension to enable synapse manipulation. We categorize these approaches on the basis of their conceptual bases and target molecules, compare their advantages and limitations and propose potential modifications to improve their effectiveness. These methods have broad utility, particularly for investigating mechanisms of synaptic function and synaptopathy.
Mammalian neurons lose the ability to regenerate their central nervous system axons as they mature during embryonic or early postnatal development. Neuronal maturation requires a transformation from a situation in which neuronal components grow and assemble to one in which these components are fixed and involved in the machinery for effective information transmission and computation. To regenerate after injury, neurons need to overcome this fixed state to reactivate their growth programme. A variety of intracellular processes involved in initiating or sustaining neuronal maturation, including the regulation of gene expression, cytoskeletal restructuring and shifts in intracellular trafficking, have been shown to prevent axon regeneration. Understanding these processes will contribute to the identification of targets to promote repair after injury or disease.
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