Special CNS Seminar

Memory is assumed to be stored in the brain as a cellular ensemble, called cell assembly, consisting of a set of neurons that is activated during learning. Optical stimulation of a cellular ensemble triggers retrieval of corresponding memory. Here we show that artificial activation of cell assemblies corresponding to two distinct events generates artificial association between initially non-related events. In the context pre-exposure and immediate shock (IS) paradigm, mice failed to associate the shock with the pre-exposed context when IS was delivered in the different context. Cells activated during the context pre-exposure and IS in hippocampal CA1 and basolateral amygdala (BLA) were targeted with channelrhodopsin-2, a light-activated cation channel. These cell were later simultaneously activated by optical stimulation. In the next day these mice showed an elevated freezing behavior, an indicator of fear response, in the pre-exposed context that was not originally associated with shock. Thus, artificial activation of distinct cell assembly, without any sensory inputs, is capable of generating an artificially associated memory. Furthermore, our finding indicates that association of distinct information is achieved through synchronous activity of distinct cell ensemble. This mechanism may underlie the memory update by incorporating a novel information into the preexisting ones to make qualitatively new memories.