The memory toolbox: how genetic manipulations and cellular imaging are transforming our understanding of learned information

Understanding memory fundamentally relies on the study of behaviour, the readout of learned information encoded in the brain. Investigating memory, therefore, requires an integrative approach that links behaviour to neural substrates. Classical methods of measuring and manipulating brain activity such as in vivo electrophysiology and pharmacological interventions have been very useful, but lack precision. Today, state-of-the-art techniques allow us to directly observe and specifically manipulate brain activity that is associated with behaviour, particularly in rodents. The use of optogenetics and chemogenetics have revolutionised the investigation of memory, in particular when coupled with activity-dependant tagging methods (e.g. engram cell labelling). Calcium imaging and especially miniaturised microscopes allowed visualisation and quantification of neuronal activity in freely behaving animals. This review will examine the contribution of these and other contemporary methodologies to conceptual progress in the neuroscience of memory.