Electrophysiological and Behavioral Approaches to the Analysis of Synaptic Tagging and Capture

Since its inception in 1997/1998, the synaptic tagging and capture hypothesis (STC) of protein synthesis-dependent synaptic plasticity has inspired a wide range of studies attempting to further our understanding of heterosynaptic plasticity and its relevance to learning and memory. In the last few years, some behavioral predictions of the STC hypothesis have been confirmed, successfully translating electrophysiology into behavior. In this chapter, we describe the principles and caveats behind experiments on STC. In electrophysiological experiments, the necessity for long stable recordings and the need for multiple convergent inputs together pose considerable technical challenges. We describe how to secure sustained recordings in acute hippocampal brain slices. We also outline how to exploit multiple input pathways to identify specific molecules that may be plasticity-related products involved in the tagging process or in the synaptic capture of long-term plasticity. In behavioral experiments, we describe novel protocols to explore whether weak encoding events that usually produce a short-lasting memory can be rescued by a closely timed but unrelated neuromodulatory experience. This phenomenon can be used to identify, within the STC framework, the mechanisms of action of memory-altering compounds. We also propose further protocols to reveal the mechanisms behind this form of neuromodulation.