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Séminaire - Inbal GoshenIlluminating Memory: An optogenetic approach to study the role of neurons and glia in memory acquisition and recall

Abstract :

Cognitive function and emotional homeostasis, and the aspiration to decipher their neuronal basis have stood at the heart of neuroscience since its inception. The complexity of the circuits underlying these processes is immense, and new techniques are necessary to provide novel efficient ways to make a significant progress in brain research. Optogenetic tools enable temporally and spatially precise in-vivo activation or inactivation of genetically defined cell populations, thus enabling deconstruction of systems that were not available for research. An example for that is our work re-examining the role of the hippocampus in remote memory.

In contrast to the prevailing theory suggesting that the following system consolidation the hippocampus becomes unnecessary for the recall of remote memories we found that even weeks after contextual conditioning, the contextual fear memory recall could be abolished by optogenetic inhibition of excitatory neurons in the CA1 region of the hippocampus- at times when all earlier studies had found no detectable influence of hippocampus. In exploring mechanisms, we found that loss of hippocampal involvement at remote timepoints depended on the timescale of hippocampal inhibition, since extending optogenetic inhibition of hippocampus to match typical pharmacological timescales converted the remote hippocampus-dependence to remote hippocampus-independence.

These findings uncovered a remarkable dynamism in the mammalian memory retrieval process, in which underlying neural circuitry adaptively shifts the default structures involved in memory—normally depending upon the hippocampus even at remote timepoints, but flexibly moving to alternate mechanisms when the hippocampus is offline on the timescale of minutes.

The power of genetic targeting can also be employed to express opsins in glia cells (especially astrocytes), which were implicated in many Neuropsychiatric disorders including Depression, schizophrenia, autism, and PTSD. However, the direct involvement of astrocytes in these disorders could not be studied because no tools were hitherto present to enable specific direct investigation of real-time astrocytic function. The scarcity of data in this field stems from the technical difficulty to specifically modulate astrocytic activity without also directly affecting the neighboring neurons. This obstacle can now be removed using Optogenetics.

Center for Brain Science / Jerusalem / Israël  

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