Prefrontal dynamics during value-based decision making

• Applicant: Professor Dr. Thomas Klausberger
• Subject Area: Experimental and Theoretical Network Neuroscience ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437610067

Success often depends on inspired choices between risk-taking for exciting achievements or perseverance with safe, incremental advancements. In this project we aim to discover how GABAergic interneurons and pyramidal cells of the prefrontal cortex cooperate in time to generate such inspired decisions based on internal valuations of probabilistic evidence. We will train mice to perform a modified-Iowa-gambling-task, successfully adjusting choices between certain-small, or possible-big rewards with changing long-term advantages. During the first funding period of this project we have shown that changes of choice strategy are reflected by abrupt changes of the neuronal firing rate in prefrontal networks. In the next funding period, we aim to discover the neuronal mechanisms underlying and initiating these change points. We will perform juxtacellular recording and labelling of distinct types of GABAergic interneurons during the value-based decision making task to determine their cellular identity and axonal projections. This will be supplemented with large-scale extracellular recordings and optotagging of multiple interneurons and pyramidal cells simultaneously. We will determine the precise firing patterns of the interneurons in relation to the population activity and in relation to the choice behavior and switches of strategy following reward experiences. We will test if the variability in choice selection, the vicariousness of the decision execution and motivational state can be explained and predicted by the firing patterns of GABAergic interneurons. Furthermore, we will detect network oscillations in the circuits of the prefrontal cortex and test their variable relation to decision making, behavioural strategy and spike timing of neurons. During the previous funding period and together with our collaborators we have established a PL-RNN model of the neuronal activity and behavior of the animal during task performance. In the upcoming funding period we aim to use this model to make specific predictions on the contribution of GABAergic interneurons to change points of concerted neuronal firing activity in the prefrontal cortex and to behavioural strategy switching. We will then test these hypothesis by optogenetically manipulating interneurons at the precise and predicted time points during task performance. The experiments proposed in this project will define the contribution of GABAergic interneurons to concerted network activity in the prefrontal cortex and to flexible and variable decision making based on internal valuation of likely outcomes.

• DFG Programme: Research Units
• Subproject of: FOR 5159: Resolving the prefrontal circuits of cognitive flexibility: Dynamic prefrontal representations of cognitive variability
• International Connection: Austria
• Partner Organisation: Fonds zur Förderung der wissenschaftlichen Forschung (FWF)