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Investigating locus coeruleus function in autism mouse models


   College of Medicine and Veterinary Medicine

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  Dr Rebecca Jordan  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Applications are invited for one 3.5 year full-time fully funded PhD studentship in the lab of Dr Rebecca Jordan within the Simons Initiative for the Developing Brain at the University of Edinburgh. SIDB (www.sidb.org.uk) is a philanthropic Centre funded by the Simons Foundation Autism Research Initiative (www.sfari.org).

Background:

Repetitive and ritualistic behaviour is a characteristic of autism spectrum disorder. Mouse models of autism also show repetitive behaviours and reduced ability to change previously learned behavioural strategies. The locus coeruleus is a neuromodulatory system releasing noradrenaline across the brain during surprising events, and is known to promote learning and cognitive flexibility. Recently, disruption of this system has been indicated in people with autism spectrum disorder [1], and in mouse models of autism [2].

Aims:

In this project we will investigate the function and role of the locus coeruleus in mouse models of autism spectrum disorder. Our specific aims are to:

  1. Generate novel paradigms to assess behavioural inflexibility and responses to surprising events.
  2. Directly compare the activity of the locus coeruleus between mouse models of autism and wild type littermates, in particular in response to surprising events.
  3. Determine whether locus coeruleus activity can be used to predict the behavioural deficits in mouse models of autism.
  4. Explore whether manipulating locus coeruleus activity can be used to mitigate the behavioural deficits in mouse models of autism.

Training outcomes:

By the end of the project, the PhD student will be trained to build and maintain mazes for freely moving mice, design behavioural tasks and experiments, use in vivo electrophysiological (and possibly optical) methods to measure activity from identified neurons, utilise optogenetic strategies to manipulate neural activity, analyse behavioural and neural recording data, and write and review scientific manuscripts.

Rationale & hypothesis:

A long standing but largely untested hypothesis is that autism is a disorder of learning predictions about the world [3], leading to excessive surprise signals in the brain known as prediction errors [4]. Our recent work shows that the locus coeruleus signals prediction errors in a general manner across the brain. We thus hypothesize that activity in the locus coeruleus can be utilised A) to determine computational deficits in autism spectrum disorder, with respect to prediction errors, B) to predict the degree of certain behavioural deficits, and C) as a potential therapy target.

Eligibility:

Applicants should have a good (2:1 or higher) undergraduate degree in a relevant subject (including, not limited to, neuroscience, biomedical sciences, molecular biology, genetics, or computational biology).

Candidates should also meet the entry requirements for admission to postgraduate programmes at the University of Edinburgh.

How to Apply:

Please email Natacia Hambakis Hatch ([Email Address Removed]) to request an application form. Once you have completed the form you should return it direct, along with your references, to Natacia Hambakis Hatch at the same email address. Please contact Rebecca Jordan as well ([Email Address Removed]) to discuss questions and the nature of your interest in the project. In the application form you should indicate why you are interested in the project and why you would be a good fit for the project.

Deadline: The deadline for applications is 16th January 2023.

Start time: The start time for the studentship is September 2023.


Funding Notes

This is a SIDB funded award. It will provide an annual stipend for 3.5 years of £20,000 per annum, plus tuition fees (including international).

References

1. Lawson, R. P., Mathys, C. & Rees, G. Nat. Neurosci. 20, 1293–1299 (2017).
2. Yin, X. et al. Nat. Neurosci. 24, 646–657 (2021).
3. Sinha, P. et al. Proc. Natl. Acad. Sci. 111, 15220–15225 (2014).
4. Jordan, R. and Keller, G.B. Neuron. 108, 1194-1206 (2020).

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