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Target specific responses of layer 6b (L6b) neurons in the mouse medial prefrontal cortex (mPFC) upon fear memory retrieval

Project description

In search of the neurons implicated in the fear memory retrieval process

Fear is a powerful emotion and one that is difficult to manage. The resilience of fear memories – the difficulty in extinguishing them once formed – likely plays a role in disorders of fear and anxiety, including post-traumatic stress disorder. Evidence points to the role of several interrelated brain regions in fear conditioning and extinction, one of them being the prefrontal cortex. The EU-funded L6b project is characterising specific neurons in the medial prefrontal cortex of behaving mice to better understand their inputs and outputs and electrophysiological responses during fear memory retrieval. The experimental data will inform an in silico model of brain circuitry involved in cognitive behaviours and psychiatric disorders. The prediction of fear-related behavioural outcomes will confirm the critical role of these neurons in the behaviours studied.

Objective

One of the fundamental challenges in neuroscience research is to understand how diverse sensory inputs leading to the specific behavioral outcome and what are the networks underlie eliciting such behaviors. This question may only be answered when measurements of structural and functional properties of individual neurons are integrated into a coherent framework, which would then allow numerically simulate (in silico) different networks to predict possible behavioral outcomes. The ‘building block’ for a network model relies on anatomical and physiological data such as neuron input, neuron output, and physiological properties collected from animal experiments. The input can be determined by reconstructing dendrites, functional properties of the neuron can be estimated by obtaining electrophysiological measurements, and output can be determined by reconstructing by their 3D axon branching pattern. Current proposed project work will address some of the building blocks such as projection targets of single neurons upon a specific behavioral expression and their presynaptic partners that are responsible for eliciting such behaviors. Specifically, I will investigate the electrophysiological properties and anatomical connectivity of L6 neurons (L6b) of the medial prefrontal cortex (mPFC) using state-of-the-art techniques and tools such as modified rabies virus labeling and neuron tracing, DREADD technology and optogenetics in a transgenic mouse line that selectively expresses Cre-recombinase in a subpopulation of layer 6b neurons. Exploring mPFC neural circuits may not only provide more in-depth insight on to its involvement in cognitive behaviors but also in a variety of psychiatric conditions such as post-traumatic stress disorders (PTSD). The outcome of this study will establish the functional role of L6b of the mouse medial prefrontal cortex to its specific involvement in eliciting specific behavioral outcomes.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 224 933,76
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 224 933,76
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