About the Project
Flexible decision-making is critical for animals and humans to adapt their behaviour to different environments and contexts. Deficits in behavioural flexibility characterise normal ageing as well as several neurological disorders, and understanding the underlying neural mechanisms is essential in developing new therapeutics. This Ph.D. studentship will study the cellular correlates of flexible decision-making in animal models of autism spectrum disorders (ASD) using a range of experimental and theoretical approaches.
Objectives and Experimental approach:
We have recently reported that task/context-switching behaviour is dependent upon specific populations of neurons in the frontal cortex which encode and convey rule-related information (Banerjee et al. Nature, 2020). However, the cellular mechanisms behind the dynamic interactions that mediate fast updating of stimulus–reward contingencies remain unclear. The Ph.D. studentship will address these questions using a range of experimental and theoretical approaches in vivo testing key hypotheses:
1) Developing novel behavioural tasks, the student will examine how neural dynamics within a distributed cognitive network in the prefrontal areas of the rodent brain contributes to evaluating reward-based computation. Special emphasis will be given to pre-limbic and infra-limbic areas including medial and lateral orbitofrontal cortex, key brain circuits for value-guided decision making.
2) The student will then use closed-loop optogenetic stimulation to manipulate oscillatory coupling before, during, and after periods of rule-reversal learning, as well as in sleep between behavioural sessions. We have recently shown that closed loop optogenetics allows precise manipulation of network dynamics, to boost or suppress oscillations at specific frequencies. These experiments will thus test the causal role of fronto-parietal-sensory network dynamics during different phases of reversal learning.
3) Dysfunctions in behavioural flexibility will then be tested using ASD animal models. The student will test whether appropriate closed-loop optogenetic stimulation can restore observed deficits in task-switching, which could pave the way for new neuromodulation therapies in ASD.
Novelty and impact:
The student will use cutting-edge neuroscience techniques in awake behaving rodents (e.g., 2-photon imaging, and optogenetics) in Banerjee lab (PNAS, 2016; Nature, 2020), complementing related neurotechnology and computational work taking place in the Jackson-lab (J Neurosci 2019) and the CANDO consortium (www.cando.ac.uk). We are a dynamic and young team based in the Henry Wellcome Building within the Faculty of Medical Sciences at Newcastle University.
This work proposed will discover crucial ‘cognitive endophenotypes’ in animal models of ASD, and test new neuromodulation therapies. This will pave the way to new behavioural assays and therapeutic strategies applicable in the clinic. Student training in this project will involve a highly synergistic UK academic, neurological, and industry team, complemented by key collaborators at Oxford (UK), MIT (USA), and ETH-Zürich (Switzerland) offering innovative training in cellular, circuit, and computational neuroscience.
Primary Advisor: Dr Abhishek Banerjee, Senior Lecturer, Newcastle University
Twitter: @abhii_mit, Homepage: www.neuronic.mit.edu
Secondary Advisor: Professor Andrew Jackson Professor, Newcastle University, CANDO website: www.cando.ac.uk/
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme and how to apply can be found on our website:
Please read additional guidance here: https://bit.ly/3kPNjoJ
Studentships commence: 1st October 2021
2) Banerjee et al. (2016) Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett Syndrome. PNAS 113(46):E7287-E7296.
3) Xu et al. (2019) Sequential neural activity in primary motor cortex during sleep. J Neurosci 39(19):3698-3712.
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