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Toward an experimental and computational approach to causal analysis in behaving zebrafish larvae

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posted on 2023-06-10, 01:44 authored by Daniel Saska
Understanding brain-wide dynamics and their relation to behaviour relies on knowledge of the interactions of the underlying functional regions in the brain. In this work, we aim to demonstrate the applicability and limitations of Granger Causality (GC) as a measure of directed functional connectivity in live zebrafish larvae, offering an alternative to commonly used undirected functional connectivity measures such as correlation. In order to acquire whole-brain datasets, we develop µSPIM: a hardware-agnostic light-sheet microscope control and acquisition toolset which provides functionality focused on functional imaging, providing an open-source alternative to existing light-sheet solutions limited to developmental imaging. Further, we present an independent closed-loop virtual reality solution which provides a exible extension to existing light-sheet or two photon microscope setups. In order to demonstrate the applicability of GC to calcium imaging data, we first apply the causal analysis to simulated spiking data generated by an integrate-and-fire model convolved with a calcium filter. We show that the directed functional connectivity reconstructed by GC follows the structural connectivity used to simulate the underlying network both in bi-variate and multi-variate settings. We identify a number of constraints on the performance of the measure in form of sampling rate, recording duration and the number of cells in the network and show that trends in the calcium data result in poor inference which can be mitigated by filtering prior to the application of GC. Next, we show that conditional GC on subsets of neurons can be used to infer directed connectivity between functionally similar neuronal circuits when analysis based on all sources is not viable due to combinatorial and computational constraints. Finally, we show that directed connectivity inferred using GC from calcium data collected in vivo from unstimulated zebrafish larvae displays functional characteristics described in prior research.

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File Version

  • Published version

Pages

140.0

Department affiliated with

  • Neuroscience Theses

Qualification level

  • doctoral

Qualification name

  • phd

Language

  • eng

Institution

University of Sussex

Full text available

  • Yes

Legacy Posted Date

2021-11-12

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