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Relating variability in prefrontal representations and dynamics to behavioral strategy changes

Subject Area Cognitive, Systems and Behavioural Neurobiology
Term since 2026
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 437610067
 
Variability is a fundamental feature of both behavior and neuronal activity. In an ever-changing environment, such variability may be beneficial by allowing animals to rapidly adjust both neuronal processing and behavioral output in response to new behavioral contingencies and environmental conditions - a hallmark of cognitive flexibility. The overall goal of the project will be to investigate how behavioral variability is manifested in dynamic neuronal representations in the mouse prefrontal cortex (PFC) and how variability in PFC activity promotes cognitive flexibility. Behavioral variability is often expressed through the use of different strategies to achieve a goal. A well-established example of this is spatial navigation, which can be accomplished using either 'egocentric' or 'allocentric' strategies relying on self-referenced or world-referenced frames, respectively. In the first funding period, we investigated how spatial working memory (SWM), a form of flexible spatial navigation, is supported by PFC activity. Building on this work, in Aims 1 and 2 of the second funding period we will determine how animals rely on egocentric versus allocentric strategies during SWM, examine intra- and inter-individual variability in strategy use, and investigate whether these strategies are reflected in different spatial representations (allocentric vs. egocentric) by PFC neurons. We will also examine how inputs from other brain regions shape these spatial representations. Whereas Aims 1 and 2 will investigate the stable activity patterns associated with distinct behavioral strategies, Aims 3 and 4 will focus on the neural dynamics underlying rapid strategy shifts. To this end, we will use a well-established task of cognitive flexibility, the attentional set-shifting task, in which rule changes require mice to shift their attention between different stimulus dimensions. We hypothesize that rule changes trigger increased neuronal variability in the PFC - representing exploration of neural state space - which facilitates sampling of behavioral options and ultimately the adoption of new behavioral strategies. We will investigate whether the magnitude of neuronal variability predicts individual differences in cognitive flexibility, and whether this variability is exhibited by PFC neuronal subpopulations with specific projection targets. In sum, the project will provide insights into how variability in behavioral strategies and PFC activity patterns supports the adaptive behavioral changes that characterize cognitive flexibility.
DFG Programme Research Units
 
 

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