ERC Starting Grant for research in memory formation and consolidation

Sadegh Nabavi has been awarded one of the prestigious ERC Starting Grants. (Photo: DANDRITE)

Figure 1. Sadegh Nabavi will use optogenetics to modify memory strength at the synaptic level to study why only some synapses, and hence memories, become permanent (Figure: Sadegh Nabavi)

Figure 2. a) Fear conditioning with optogenetics. Diagram of rat’s fear memory circuit receiving optogenetically driven input stimulation (laser) paired with a shock (left). Animal is tested one day later (right) by optical activation of the input (blue). Time plot shows normalized number of lever presses (1 min bins) to a previously learned cued lever-press task. b) LTD inactivates memory. In vivo field response in lateral amygdala to single optical stimulus (left) before and after LTD induction (1Hz). Animal is tested one day later (right). c) LTP reactivates memory. Same as b) except animal receives an LTP protocol (100Hz). (Figure: Sadegh Nabavi, published in Nature (Nabavi et al., 2014))

20 November 2015 by Karen Bech

The ERC project will address a number of fundamental questions in neuroscience that focus on memory formation and consolidation at the synaptic and circuit levels.

Memories are formed by changes in the strength of connections between neurons, a process known as synaptic plasticity. In a recent study Sadegh Nabavi and his former colleges demonstrated this conclusively by showing that one can generate a memory and then repeatedly turn off and on this memory simply by weakening and strengthening synapses, known as Long Term Depression (LTD) and Long Term Potentiation (LTP) induction (see figure 2). The immediate question following this study is why some memories last while others are lost soon after they are formed. This question, which concerns one of the fundamental issues in memory research known as memory consolidation, is the subject of Sadegh Nabavi's ERC Starting Grant.

As we all know from our daily experiences, we can recall trivial events temporarily but they gradually fade from our memory. However, when a salient event occurs before or after an insignificant event, we are able to recall details from the insignificant event, which otherwise would have been forgotten. There is a tremendous survival benefit to this. We can detect subtle signals for a threat (or reward) that may lie around the corner, because we still remember the details of our previous experience. However, the downside to this mechanism can be seen in post-traumatic stress disorders, where a traumatic event can haunt a person for life. How does an emotionally charged event lead to an unmemorable event becoming a permanent memory by virtue of temporal linkage?

Application of ground-breaking methods

In his efforts to answer these questions, Sadegh Nabavi will examine memories at their building blocks, the synapses, and study whether stability of memories is reflected in the stability of their synaptic strength. If so, what are the molecular mechanisms by which only some synapses, and hence memories, become permanent? To this end he will use optogenetics to modify memory strength at the synaptic level. In vitro and in vivo electrophysiology combined with behavioral studies are the primary methods used in his research group to detect and quantify changes in the synaptic as well as memory strength. Finally, to identify the underlying molecular mechanisms, Sadegh Nabavi's research group will benefit from transgenic animals, in vitro/in vivo imaging and proteomics.

Sadegh Nabavi has already published several articles on synaptic plasticity and memory formation in prestigious journals such as Neuron, PNAS, and Nature.

The European Research Council (ERC) provides funding for ground-breaking international research projects of scientific excellence in all subjects and fields of research.

For more information, please contact

Sadegh Nabavi
Group Leader at DANDRITE (the Danish Research Institute of Translational Neuroscience)
Associate professor at Dept. Molecular Biology and Genetics
Aarhus University

Email: snabavi@dandrite.au.dk
Group website: www.dandrite.au.dk/nabavi