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Visualizing synapses during sleep and wake states in zebrafish larvae

Suppermpool, Anya; (2021) Visualizing synapses during sleep and wake states in zebrafish larvae. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Sleep is a behavioural state that is conserved throughout the animal kingdom. However, the function of sleep is still unknown. The Synaptic Homeostasis Hypothesis (SHY) proposes that the increased synaptic strength during wakefulness must be renormalized by sleep. Some evidence from both rodents and Drosophila in favour of SHY include observed increases in synaptic protein levels during waking and a population-wide reduction of synapse size during sleep. However, the most powerful test for SHY—directly observing synapse dynamics in the same neuron across sleep/wake states—has not been performed to date. In this project, we modified a genetic marker for synapses, Fibronectin Intrabodies Generated with mRNA display (FingRs), to visualize both excitatory and inhibitory synapses in vivo in the optically translucent zebrafish. We demonstrated that FingRs label bona fide synapses with high fidelity and dynamically change over time in vivo. Using FingRs to image synapse dynamics across multiple day/night cycles, we found that at the populational level, net excitatory synapse number of optic tectal neurons increased during the day phase and decreased over night, consistent with the predictions of SHY. However, individual neuron synapse trajectories are diverse, such that only certain subtypes of tectal cells are strongly rhythmic across the day. While synapse dynamics in tectal cells do not correlate with prior total sleep duration or waking activity, extended wakefulness acutely increases synapse number, with a reduction in synapses in the subsequent sleep period. Together, these data indicate that day-night rhythms in synapse number are influenced by the sleep-wake cycle, but this is not observed universally in all neurons.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Visualizing synapses during sleep and wake states in zebrafish larvae
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10139746
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