Mostafa Nashaat, Hatem Oraby, Flutra Krasniqi, Sek Teng Goh-Sauerbier, Marion Bosc, Sandra Koerner, Sedef Karayel, Adam Kepecs, Matthew E. Larkum

Not all decisions are created equal; factors such as the difficulties or associated costs affect the time spent to make decisions. This is variously interpreted as speed/accuracy, fast/slow, or impulsivity/deliberateness tradeoffs according to different models of behaviour^1–5. Regardless, it is generally assumed that decision latency reflects the neural mechanisms underlying behavioural strategy and cognitive investment. However, such investigations have been difficult in mice which are consistently impulsive. Here, we show that manipulating cost, using a novel floating-platform paradigm, overcomes the natural impulsivity of mice, more closely matching human behaviour. Furthermore, this approach allowed us simultaneously to measure the flow of activity from medial to lateral frontal cortex (MFC→LFC) and record sequences of single neuron activity with 2-photon imaging. Surprisingly, MFC display a different mode of operation, with high vulnerability to optical inhibition compared to LFC. Furthermore, the balance in choice coding at the beginning of sequences in MFC correlated with trial history and behavioural strategy. We found that for optimal performance, slow sequences in MFC showed declining numbers of active neurons whereas the opposite was true in LFC. Our results suggest that while LFC acts as an integrative motor threshold, MFC plays a larger cognitive role in the selection and timing of decisions than previously thought. Our study offers a methodological and mechanistic framework in mouse frontal cortex to understand the neural basis of voluntary decision making.

bioRxiv (2024)