How the brain prevents the co-formation of competing memories

• Applicant: Professor Dr. David Owald
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561174579

Understanding how distinct forms of memories are stored and integrated to guide and trigger appropriate behavior is a fundamental challenge of the neurosciences. This question can be investigated when considering classical or operant conditioning. When a cue consistently predicts an outcome regardless of an individual's behavior, a classically conditioned association is formed. When an individual's actions directly influence the occurrence of an outcome, operant conditioning occurs. Classical and operant conditioning are thought of as distinct forms of learning, involving different brain structures, that are, nevertheless, additive. However, classical and operant conditioning can result in different behavioral responses even if the environmental stimuli and reinforces are similar. Thus, the two forms of memories can encode for a conflicting behavioral output, and this can result in an inadequate behavioral response to a salient cue. How the brain prevents the co-formation of competing memories is currently unknown and the exact interplay between their underlying neuronal circuits remains incomplete. The main objective of this proposal is to examine how the brain prevents the formation of competing memories that lead to mutual exclusive behaviors. To address this objective, we will study the Drosophila olfactory system. Flies can be conditioned both using classical and operant protocols, while memory traces in the mushroom body (MB), the olfactory learning and memory center, can be easily tracked and there is genetic accessibility to different parts of the neuronal circuits. Indeed, our preliminary results locate classically and operantly conditioned memory traces and show that the two memories cannot be formed simultaneously and are non-additive. Furthermore, our data suggests that plasticity of odor responses in the central complex (CX), the navigation center in the fly brain, is crucial for gating which memory is formed in the MB. We will use a multidisciplinary approach of behavior, 2-photon imaging and genetics to examine the mechanisms underlying CX odor response plasticity and its importance to the gating of classical and operant memories, how this information arrives from CX to MB, and how another modality, vision, is integrated in this process. Our data indicate that classical and operant memories are non-additive and mutually exclusive. While not excluding later interference or transfer between the traces, this separation in either or between operant and classical conditioning provides a new avenue of solving how the same cues can lead to mutually exclusive behaviors. If successful, this project is therefore expected to significantly influence the way the field thinks about memory formation.

• DFG Programme: Research Grants
• International Connection: Israel
• Partner Organisation: The Israel Science Foundation
• Cooperation Partner: Professor Moshe Parnas, Ph.D.