Rewiring the valence encoded by experience: where is the plasticity

NOVEMBER 24TH, 2017 - 11 AM

Roger RedondoRoche Innovation Center, Basel, Switzerland.

Location: Auditorium C7, building C, 7th floor, Jussieu Campus.

Summary: During memory formation, experience binds together the contextual representation of where an event takes place with the emotion that accompanies it. Current learning and memory models postulate that during recall, reactivation of sensory representations have access to motor and hormonal output centers of the brain. A few years ago, we, the Tonegawa laboratory, showed that neurons in the Dentate Gyrus (DG) of the hippocampus that upregulate the immediate early gene c-fos during the formation of a contextual fear memory can later drive the appropriate fear response. In 2013, we showed that the artificial reactivation of a DG neuronal ensemble encoding a neutral context while the mice experienced fear could give new meaning to such context. Inspired by these findings, we asked ourselves: Is this circuit and technology limited to fear memories or can it also be affect memories linked to positive emotions? Where is the DG neuronal output associated with the emotion it drives? And finally, can such association be artificially changed? By applying a multidisciplinary approach that includes immunohistochemistry, optogenetics and novel behavioral paradigms, I will present a series of studies aimed at targeting plasticity to the circuits that form fear and reward associations. As a consequence of such plasticity, the valence associated with the DG neuronal ensembles was reversed from negative to positive and vice versa. The same plasticity was absent in amygdala outputs. During my presentation, I will introduce the latest data on where in this memory circuit there is the plasticity necessary to bind experience to value. I will also introduce how circuit dissection technologies are being applied in industry to develop better therapies.

Dr. Roger Redondo studied Biology at the University of Barcelona before moving to the Unites States to learn electrophysiology in sea slugs during his Master’s of Science. In 2003, he started his PhD in Neuroscience at the University of Edinburgh under the mentorship of Prof. Richard GM Morris. There, Dr. Redondo demonstrated the distinct roles of CaMKII and CaMKK in long-term potentiation (LTP) and re-formulated the Synaptic Tagging and Capture Hypothesis. In 2010, he joined the Picower Institute for Learning and Memory as a postdoctoral associate in Prof. Tonegawa’s laboratory. There, he contributed to the development of an inducible and activity dependent optogenetic labeling system that led to the first demonstration of artificial memory recall by neuronal stimulation. Next, he co-authored a study that revealed how the internal representation of a contextual memory could be artificially linked to experience. This research was very suggestive that such ‘engram’ technology had access to the circuits that assigned valence to contextual representations. Dr. Redondo’s most recent work has used a combination of imaging, optogenetic and behavioral procedures to target plasticity to the circuits underlying learning and memory. Dr. Redondo is now a Lab Head at Hoffmann-La Roche bringing circuit dissection capabilities to drug discovery.