Neural mechanisms of perceptual decision-making in the fruit fly

A mobile organism is faced with the challenge of having to decide, moment by moment, its next course of action. Despite extensive efforts in mapping decision-making circuits across many species, the current understanding of neural mechanisms underlying the decision process remains scarce. Fruit flies can perform an odour discrimination task with difficulty-dependent reaction times and choice accuracies, in a framework well-described by a process of evidence accumulation to bound. A subset of third-order olfactory neurons, the αβ core Kenyon cells (αβc KCs), appears to act as a temporal integrator of sensory information, encoding the amount of summed evidence in their subthreshold voltage. However, explicit demonstration of a causal role of these neurons is lacking. Combining molecular cloning, patch-clamp electrophysiology, closed-loop optogenetics, and drift-diffusion modelling, I establish a causal relationship between the neural activity in αβc KCs and the fly's olfactory decision-making. First, I discover that a short motif from AMPA receptors can target the optogenetic activator to the somatodendritic compartment of the cell, enabling the optical injection of small dendritic currents. I also modify the genetic construct of the optogenetic inhibitor such that its expression is restricted to the decision-relevant neurons. Second, the functionality of these tools is characterised by whole-cell recordings of αβc KCs. Third, I bidirectionally manipulate the activity of these neurons during the perceptual task to test for behavioural consequences in speed and accuracy. I find that photostimulation quickens reaction times as a function of odour contrast and light intensity. This is mainly explained by a reduction of the bound height in drift-diffusion models, consistent with the representation of the integrated amount, rather than the momentary level, of evidence in αβc KCs. This work sheds light on the mechanisms by which decision-making is implemented in a biological substrate.