EphrinB2 modulation of neuronal morphology and ensemble activity to encode long-term memory: an integrated theory-experiment approach

• Applicants: Professor Jan Gründemann, Ph.D.; Professorin Dr. Tatjana Tchumatchenko
• Subject Area: Experimental and Theoretical Network Neuroscience ; Cognitive, Systems and Behavioural Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559314332

The storage of long-term memories is important for our mental well-being, social interactions and survival. Long-term memory formation depends on alterations in synaptic transmission efficacy between neurons and the formation of new neuronal ensembles with memory-specific activity patterns. These adaptive activity patterns in defined neuronal ensembles are thought to encode long-term memories and allow an organism to modify its behavior and respond differently to the environment. However, so far, we only know very little about the mechanisms that underlie and trigger changes in ensemble activity during long-term memory formation. In this proposal, we will take a step towards this goal and will investigate how ephrinB2 affects the formation of neuronal ensembles for long-term memory formation in amygdala circuits. It has been shown previously that ephrinB2 deletion in the amygdala of mice impairs the formation of long-term memory, but not short-term memory upon associative learning. Furthermore, injections of ephrinB2 into the amygdala of wildtype animals during learning enhance specifically the formation of long-term memories. Nevertheless, the effect of ephrinB2 on the neuronal population code during memory formation and retrieval remains unknown. Here we will combine the expertise of three research laboratories to study how ephrinB2 affects the large-scale neuronal activity of defined amygdala neurons during long-term memory formation with the help of state-of-the-art tools including viral knock-down of ephrinB2 expression, deep-brain imaging with miniature microscopes, structural analysis of neuronal morphology and computational neuroscience approaches. We will furthermore test how ephrinB2 in glial cells impacts amygdala coding during learning and long-term memory assignment. Finally, we will test how ephrinB2 can boost memory formation via changes in the neuronal code and construct a computational model based on our findings to gain mechanistic intuitions about ephrinB2 in neuronal ensemble coding and generate hypotheses for future experiments.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Professor Dr. Raphael Lamprecht