<B DATA-STRINGIFY-TYPE="BOLD">FUNCTIONAL ANALYSIS OF VLOFC INTERNEURONS DURING DECISION-MAKING UNDER UNEXPECTED UNCERTAINTY</B>

Aim: The ventrolateral orbitofrontal cortex (vlOFC) is recognized as a core region supporting flexible behavior. Recent works consistently indicate that thalamic inputs to prefrontal areas are important for cognitive functions and that these thalamic inputs target both pyramidal and local interneurons. This study therefore aimed to examine the functional contribution of inhibitory neurons in the vlOFC to decision-making.
Methods: Exploration and exploitation behaviors were assessed using an instrumental three-armed bandit task with distinctive probabilistic action–outcome contingencies defining good or bad options. The activity vlOFC inhibitory neurons was manipulated either specifically (with PV-Cre animals to target PV neurons specifically) or more generally using a mAGNET AAV to target all inhibitory interneurons. Fiber photometry recordings were also performed to examine activity dynamics synchronized with decision-making behavior. Anatomical connectivity between the mediodorsal thalamus (MD) and vlOFC-PV neurons was assessed using AAV-based transsynaptic labeling.
Results: Manipulation of vlOFC-PV interneuron activity did not affect behavioral performance in a task with stable, well-learned contingencies. However, under conditions of increased environmental noise (i.e., heightened task demand), chemogenetic activation of vlOFC-PV interneurons accelerated behavioral adaptation.
Fiber photometry recordings revealed that vlOFC-PV interneurons exhibit distinct activity dynamics compared to vlOFC pyramidal neurons during decision-making. Anatomical tracing further identified monosynaptic inputs from the MD to vlOFC-PV interneurons.
Conclusions: These results demonstrate that vlOFC interneuron activity influences exploration and exploitation behavior under changing environmental conditions and strongly suggest the need for further detailed functional analyses of MD to vlOFC interneuron projections.