Periodic Reporting for period 3 - RECENT-TO-REMOTE (Remote Memory Consolidation Based on Activity, Connectivity and Stability; Contribution of Neurons and Astrocytes.)
Okres sprawozdawczy: 2021-11-01 do 2023-04-30
This project aims to address these questions, under the novel hypothesis that hippocampal neurons prioritized for remote consolidation are more likely to be connected to the anterior cingulate cortex (ACC), which in turn will be recruited for the long-term storage of memory. I further suggest a mechanistic investigation of the fundamental theoretical framework of 'systems consolidation' describing the transition from recent to remote memory, hypothesizing it is implemented by continuous interactions between brain regions, e.g. the hippocampus and the ACC. Finally, I propose a novel function for hippocampal astrocytes in recent and remote memory, ensemble allocation, and possibly in the independent representation of memory features. We are testing these hypotheses in a comprehensive by combining complementary conceptual and technical approaches.
A. The parts of the project investigating the role of astrocytes in projection-specific effects on memory acquisition (Aim 3A, 3B) and the role of the CA1 and ACC projection in remote memory acquisition (Aim 2B, 2C) were completed, and the paper describing the findings was accepted for publication at Nature Neuroscience.
B. The part of the project investigating the role of astrocytes in ensemble selection based on cFos (part Aim of 3A) expression was finished, without any exciting findings on this specific question. We will continue investigating this question using tools with finer temporal resolution (see section D below). Nevertheless, this project required us to create an elaborate map of the mutual anatomy of astrocytes and neurons in the hippocampus, and a manuscript describing these findings is currently under review at Neuron.
C. We have imaged astrocytic activity in mice navigating a virtual environment (Aim 3C), and made very exciting discoveries: whereas single astrocytes do not encode specific locations (as opposed to neurons), it is possible to design an encoder that will infer the location of the mouse based on the activity of the astrocytic population. Furthermore, there is a clear difference in astrocytic activity when mice are navigating a familiar or a novel environment. A manuscript describing the results of these experiments is now in writing.
D. Our 2-photon microscope was upgraded (by ERC funding) to allow parallel 2-channel imaging of astrocytes and neurons. We are now calibrating co-expression of indicators in these two populations.
Investigation of the interactions between neurons and astrocytes, using simultaneous imaging in behaving animals, will deepen our understanding of their unique involvement during cognitive tasks. We will track the activity of neurons and nearby astrocytes and test the correlations between their temporal activity patterns, and how it relates to external features of the environment and various aspects of behaviour.