eprintid: 10147019 rev_number: 10 eprint_status: archive userid: 699 dir: disk0/10/14/70/19 datestamp: 2022-06-09 07:05:41 lastmod: 2022-06-09 07:05:41 status_changed: 2022-06-09 07:05:41 type: thesis metadata_visibility: show sword_depositor: 699 creators_name: Phillips, Matthew G. title: Navigational Strategies and the Role of the Hippocampus in Mouse Escape Behaviour ispublished: unpub divisions: C08 divisions: D75 divisions: B02 divisions: UCL note: 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. abstract: Executing appropriate defensive actions is vital for survival. In mice, imminent threat elicits fast and accurate escape behaviour that relies on a rapidly formed spatial memory to reach shelter locations. I investigated the navigational strategies used by mice to navigate to safety upon imminent threat, and the role of the hippocampal formation – classically associated with spatial representations – in guiding escape navigation. Through a series of behavioural experiments designed to distinguish between navigational strategies guiding escape, I found that while flight was consistent during the the first 800ms across light and dark conditions, visual cues enabled faster, more efficient escape trajectories later on in flight, suggesting escape has two phases: orienting and accelerating towards the shelter, relying on a memorised vector; and a second phase using vision to refine escape trajectories. Accordingly, I found that path integration was necessary for navigation in the dark, but not in the light. I next investigated the dependency of escape on brain structures associated with spatial representation in the hippocampal formation. An abrupt lesion targeted to the hippocampus using ibotenic acid disrupted escape navigation. A more targeted lesion of the primary hippocampal output - an infusion of muscimol into the subiculum – also led to a disruption of escape navigation and an increased propensity to freeze in response to looming visual stimuli. Finally, while disrupting neural activity in the subiculum by stimulating with channelrhodopsin reduced acceleration, this effect was present with optogenetic stimulation alone, precluding any firm conclusions from these experiments with respect to escape navigation. Together, these data further our knowledge of defensive behaviours in mice by implicating high-level spatial representations of the environment in guiding escape navigation, identifying behavioural signatures of navigational strategies requiring these representations, and showing the dependency of escape navigation on brain regions associated with spatial representations. date: 2022-04-28 date_type: published oa_status: green full_text_type: other thesis_class: doctoral_open thesis_award: Ph.D language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1950014 lyricists_name: Phillips, Matthew lyricists_id: MGPHI93 actors_name: Phillips, Matthew actors_name: Zahnhausen-Stuber, Petra actors_id: MGPHI93 actors_id: PMZAH20 actors_role: owner actors_role: impersonator full_text_status: public pages: 141 institution: UCL (University College London) department: The Sainsbury Wellcome Centre thesis_type: Doctoral citation: Phillips, Matthew G.; (2022) Navigational Strategies and the Role of the Hippocampus in Mouse Escape Behaviour. Doctoral thesis (Ph.D), UCL (University College London). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10147019/1/Phillips_PhD_Thesis_corrected.pdf