Zuccarini, Giulia; (2025) Neural circuits underlying generation of hunting sequences in larval zebrafish. Doctoral thesis (Ph.D), UCL (University College London).

Text GZuccarini_Thesis_PostViva.pdf - Accepted Version Access restricted to UCL open access staff until 1 August 2026. Download (22MB)

Abstract

Animals accomplish complex goal-directed behaviours by chaining simpler motor actions into behavioural sequences, requiring context-specific action selection for success. How the brain organises such action sequences remains poorly understood. Hunting in larval zebrafish offers a powerful model to study these processes: it is an innate, visually guided behaviour composed of a sequence of specialised motor outputs dynamically selected and tuned in response to changing visual input. Previous work has identified a population of pretectal neurons that command hunting initiation, and neurons in the nucleus isthmi required for the maintenance of the behaviour. However, little is known about the neural dynamics of these populations during extended hunting sequences, or how their activity relates to brain-wide circuits expected to control hunting behaviour. By combining a closed-loop virtual hunting assay with two-photon functional calcium imaging, I recorded neural activity during prolonged virtual hunting responses. I detected sustained activity that scales with the length of the hunting sequence in the AF7-Pretectum, where hunting command neurons are located, and identified a previously undescribed population of neurons in the intermediate hypothalamus (IH) that exhibits the same activity pattern. Circuit tracing experiments revealed that these hypothalamic neurons send axonal projections to the AF7-Pretectum, confirming that the two regions are anatomically connected. By removing these connections through laser ablation, I confirmed that, while the hypothalamic-pretectal pathway is not necessary for hunting initiation, it plays a crucial role in the successful completion of the behaviour. Freely hunting ablated larvae show a significant reduction in the number of captured prey due to increased miss strikes. Functional imaging reveals attenuated, but not abolished, activity in the AF7-Pretectum. These findings point to the IH-AF7 pathway as a new player in the neural circuit controlling hunting behaviour, supporting a role in sustaining neural dynamics required for successful hunting sequence execution.

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