Context-dependent modulation of memory systems

• Applicant: Dr. Lisa Scheunemann
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495407463

A key function of the brain is to decide which information is relevant enough to be stored as a stable memory. The molecular and circuit mechanisms that gate memory formation by inhibiting the storage of irrelevant information remain yet largely elusive. To evaluate an experience correctly, it is important to integrate the external setting (where am I) with the internal state (what do I need). Pathological perturbation of this filtering process can have catastrophic consequences for cognitive functions as well as adaptive decision making. Thus, my research aims at understanding how memory suppressor mechanisms prevent inappropriate information being processed into long-lasting memories to ensure adequate behavior. Furthermore, I will reveal how these gating mechanisms can be controlled by contextual and state-dependent processes potentially including evolutionary older – neuroendocrine – brain regions. Deciphering the detailed mechanisms of memory suppression remains challenging, largely due to the complexity of nervous systems. To reveal how neuronal suppressor systems could link physiological and cognitive functions, my proposal uses genetic, behavioral and in vivo imaging approaches in the fruit fly Drosophila melanogaster, taking advantage of the rich genetic toolbox, versatile behavioral assays and a numerical simpler brain that is experimentally easy to access. In previous work, I have identified a memory suppressor mechanism by serotonergic neurons (specifically the SPN "Serotonergic Projection Neurons") that acts outside of the fly’s memory center. This “memory checkpoint” sustains a default inhibition of memory consolidation controlled by phosphodiesterase (PDE)-mediated suppression of neuronal activity in the SPN. Serotonin acts as a neuromodulator that can alter sensory processing, adapt to the internal state and influences the perception of social context across species. A comprehensive understanding of how serotonin signals intersect with memory gating mechanisms is still missing. Importantly, my data as well as results from other studies indicate that the serotonergic system including the SPNs take part of a neuroendocrine circuit directly involved in the regulation of innate behavior like food intake, sleep or reproduction. Thus, I propose the identified serotonergic neurons and interacting network perform hypothalamic-like functions in the insect brain and potentially integrate physiological and behavioral states into memory gating mechanisms. Revealing how PDE-dependent inhibition of serotonergic neurons is released specifically in relevant contexts to allow the formation of a stable memory could identify generic design principles of how behavioral- and memory-dependent plasticity interact. Knowing these concepts will permit hypothesis-driven screening for risk factors leading to maladapted behavior as seen in addiction and anxiety disorders, on the one hand, and cognitive decline, on the other.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: 2-Photonen Mikroskop
• Instrumentation Group: 5090 Spezialmikroskope