Molecular and cellular mechanisms of memory consolidation in the neocortex

ⓘ Image creditPhoto courtesy of A10 Members

In the second round of the CRC1315, we established that memory consolidation in a µStimulation-based learning paradigm requires local mTORC1 signaling and protein synthesis in these dendrites. This provides a rare opportunity to study the molecular basis of memory at a defined subcellular site in a well-controlled behavioral setting. In this third phase, we will refine the µStim task by introducing parameter-dependent reward structures to pinpoint when and where mTORC1 activity is needed. The refinement of the µStim task will be one in collaboration with the A04 project. We will also use TRAP2-based activity marking and enriched environment paradigms to identify and label neurons involved in memory traces. At the subcellular level, we will investigate how local protein synthesis affects dendritic structure and function. Specifically, we will study how lysosome positioning, Wnt signaling, and cytoskeletal remodeling interact with mTORC1 at shaft synapses to support synaptic clustering and dendritic excitability. Techniques will include live imaging, correlative electron microscopy, and RiboTag profiling to identify newly synthesized proteins. Together, these experiments will help uncover how memory-related signals are integrated and stabilized at the level of individual dendrites.

Image: Courtesy of A10 members

Archive – A10 (SFB1315/2)

ⓘ Image creditImage courtesy of A10

Graphical abstract: Using µStim-based learning, project A10 explores how local mTORC1 signaling, lysosome positioning, and cytoskeletal remodeling contribute to memory consolidation at the level of tuft dendrites in the neocortex.