Abstract
The most commonly studied form of synaptic plasticity is long-term potentiation (LTP). Over the last 15 years, it has been possible to induce structural and functional LTP in dendritic spines using two-photon glutamate uncaging, allowing for studying the signaling mechanisms of LTP with single synapse resolution. In this review, we compare different stimulation methods to induce single synapse LTP and discuss how LTP is expressed. We summarize the underlying signaling mechanisms that have been studied with high spatiotemporal resolution. Finally, we discuss how LTP in a single synapse can be affected by excitatory and inhibitory synapses nearby. We argue that single synapse LTP is highly dependent on context: the choice of induction method, the history of the dendritic spine and the dendritic vicinity crucially affect signaling pathways and expression of single synapse LTP.
Highlights
Synaptic plasticity is the fundamental cellular correlate of learning
The goal of this review is to summarize and compare studies that used two-photon glutamate uncaging to gain insight into single synapse long-term potentiation (LTP) signaling pathways
Thanks to tremendous technological advances, signaling pathways involved in single synapse LTP are studied with spectacularly high spatial and temporal resolution
Summary
Synaptic plasticity is the fundamental cellular correlate of learning. By the strengthening and weakening of specific connections, information processing in the brain is changed and memories are formed. As first identified in the rabbit brain by Bliss and Lømo (1973), repeatedly stimulating synapses can lead to long lasting enhancement of synaptic strength. Electrophysiological recordings and biochemical analysis of the underlying signaling pathways have provided significant insights into the mechanisms of LTP (Malenka and Bear, 2004; Citri and Malenka, 2008; Sjöström et al, 2008; Mayford et al, 2012; Bliss and Collingridge, 2013; Herring and Nicoll, 2016; Nicoll, 2017; Diering and Huganir, 2018) This way of inducing LTP does not reflect the physiological situation very well. Synaptic inputs are usually not synchronously active in such large numbers, and synaptic plasticity presumably takes place at the scale of individual or small groups of synapses
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