Emotional tagging—A simple hypothesis in a complex reality Jorge A. Bergado a , Morgan Lucas b , Gal Richter-Levin b,c,d, * a Centro Internacional de Restauracion Neurologica (CIREN), La Habana, Cuba b Department of Psychology, University of Haifa, Haifa, Israel c Department of Neurobiology, University of Haifa, Haifa, Israel d The Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel Contents 1. Introduction ...................................................................................................... 65 2. Synaptic plasticity and the mechanisms of memory ...................................................................... 65 2.1. Synaptic tagging ............................................................................................. 67 2.2. Emotional modulation of memory ............................................................................... 67 2.3. Emotional modulation of LTP ................................................................................... 68 3. Complexity of the emotional tagging concept ........................................................................... 68 3.1. Spatial complexity ........................................................................................... 69 3.1.1. The effect of stress and amygdala activation on CA1 and DG LTP .............................................. 69 3.1.2. Effect of amygdala activation on other neuronal structures ................................................... 69 3.2. Temporal complexity ......................................................................................... 70 3.2.1. ‘‘Short’’-term effects (minutes vs. hours) .................................................................. 70 3.2.2. Personal history and the interaction between stress and brain development ..................................... 70 Progress in Neurobiology 94 (2011) 64–76 ARTICLE INFO Article history: Received 8 June 2010 Received in revised form 15 February 2011 Accepted 15 March 2011 Available online 22 March 2011 Keywords: Emotional memory Amygdala Hippocampus LTP Synaptic tag ABSTRACT At the psychological level, the notion that emotional events may be better remembered is a long accepted view. Its translation into neurobiological mechanisms has led to the proposal of the ‘emotional tag’ concept, according to which, the activation of the amygdala by emotionality would result in modulation of neural plasticity in brain regions (e.g. hippocampus) involved in forming memory of the emotional event. In line with this idea, amygdala activation (by electrical stimulation or exposure to an emotional event) has been demonstrated to affect synaptic plasticity in the hippocampus. Furthermore, the mechanisms associated with the formation of a ‘synaptic tag’, which is a mechanism proposed to explain the specificity of synaptic plasticity, could subserve the effects of the ‘emotional tag’ on synaptic plasticity in the hippocampus. The literature reviewed here supports this view but points also to additional factors that should be taken into consideration, such as intensity, duration, controllability of the emotional experience, age of exposure and relations between the emotional aspects of the experience and the event-to-be- remembered. These factors do not only affect the behavioral outcome of the stressful experience but also find their expression in variations in the neuronal and biochemical pathways that are activated, and in the way those will interact with memory formation mechanisms. While adding complexity to the notion of the ‘emotional tag’, taking such factors into consideration is likely to bring us closer to elucidating the neural mechanisms involved in emotional memory modulation and to our understanding of the neurobiology of associated disorders, such as PTSD. ß 2011 Elsevier Ltd. All rights reserved. Abbreviations: LTD, long-term depression; LTP, long-term potentiation; E-LTP, early-LTP; L-LTP, late-LTP; DG, dentate gyrus; PRPs, plasticity-related proteins; MAPK, mitogen-activated kinase; MFB, medial forebrain bundle; LA, lateral amygdala; B, basal amygdala; BLA, the basolateral complex; CE, central amygdala; US, unconditioned stimulus; CS, conditioned stimulus; PTSD, post-traumatic stress disorder; ELS, early-life stress; vmPFC, ventro-medial prefrontal cortex. * Corresponding author at: Department of Neurobiology, University of Haifa, Mount Carmel, 31905 Haifa, Israel. Tel.: +972 48240962; fax: +972 48288578. E-mail address: galrichterlevin@gmail.com (G. Richter-Levin). Contents lists available at ScienceDirect Progress in Neurobiology journal homepage: www.elsevier.com/locate/pneurobio 0301-0082/$ – see front matter ß 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.pneurobio.2011.03.004