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Model of theta frequency perturbations and contextual fear memory

Castegnetti, G; Bush, D; Bach, DR; (2021) Model of theta frequency perturbations and contextual fear memory. Hippocampus 10.1002/hipo.23307. (In press). Green open access

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Abstract

Theta oscillations in the hippocampal local field potential (LFP) appear during translational movement and arousal, modulate the activity of principal cells, and are associated with spatial cognition and episodic memory function. All known anxiolytics slightly but consistently reduce hippocampal theta frequency. However, whether this electrophysiological effect is mechanistically related to the decreased behavioral expression of anxiety is currently unclear. Here, we propose that a reduction in theta frequency affects synaptic plasticity and mnemonic function and that this can explain the reduction in anxiety behavior. We test this hypothesis in a biophysical model of contextual fear conditioning. First, we confirm that our model reproduces previous empirical results regarding the dependence of synaptic plasticity on presynaptic firing rate. Next, we investigate how theta frequency during contextual conditioning impacts learning. These simulations demonstrate that learned associations between threat and context are attenuated when learning takes place under reduced theta frequency. Additionally, our simulations demonstrate that learned associations result in increased theta activity in the amygdala, consistent with empirical data. In summary, we propose a mechanism that can account for the behavioral effect of anxiolytics by impairing the integration of threat attributes of an environment into the cognitive map due to reduced synaptic potentiation.

Type: Article
Title: Model of theta frequency perturbations and contextual fear memory
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hipo.23307
Publisher version: https://doi.org/10.1002/hipo.23307
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: anxiety, anxiolytic, contextual fear, fear recall, theta rhythm
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10121418
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