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Understanding how interneurons in medial prefrontal cortex control associative recognition memory


Project Description

Supervisors: Zafar Bashir (Bristol), Clea Warburton (Bristol), John Aggleton (Cardiff)
The medial prefrontal cortex (mPFC) forms the hub of a brain circuit critical for associative recognition memory. The role of mPFC inhibitory interneurons in associative memory is not known. This project will combine behavioural, opto/chemogenetic, circuit mapping and synaptic physiology techniques to determine how different interneurons control different phases of associative memory. The aims of the project will be achieved by the student working within a highly collaborative grouping of postdocs, PhD students and technicians across Bristol and Cardiff.
The medial prefrontal cortex (mPFC) forms the centre of a brain circuit essential for associative recognition memory. Regions including the hippocampus (HPC), nucleus reuniens (NR) and medial dorsal thalamus (MD) have extensive projections to mPFC, with each connection required for learning. While much work has focused on excitatory neurons in learning, there is remarkably little understanding of the roles of interneurons in associative memory. This project aims to determine (i) whether interneurons control different phases of associative memory, (ii) the distribution and/or convergence onto mPFC interneurons of inputs from the different nodes of the circuit (HPC,NR,MD), (iii) how these inputs control interneuron and circuit activity.
(i) This project will begin by investigating the roles of SOM interneurons in encoding and retrieval of associative memory. This functional component of the project will use viral targeting of inhibitory DREADDs to selectively inhibit SOM mPFC interneurons in SOM-cre mice during the encoding and retrieval of recognition memory.
(ii) Determining whether inputs from different regions of the memory circuit converge onto SOM interneurons will be achieved by examining co-localisation of SOM labelled interneurons with separate anterograde markers injected into 2 regions of the memory circuit at a time.
(iii) Optogenetic activation of inputs from different regions of the memory circuit will be used to examine transmission and plasticity at these synaptic inputs onto SOM-interneurons. Viral delivery of ChR2 will be performed in the input brain regions then whole cell electrophysiological recordings will be carried out from interneurons in mPFC slice preparations from SOM mice.

Funding Notes

DEADLINE: Applications close at 5.00pm on Friday 25th NOVEMBER.

A 3.5 year funded studentship by the GW4BioMed MRC Doctoral Training Partnership. Full UK/EU tuition fees, a stipend matching UK Research Council Minimum (£15,009 p.a. for 2019/20, updated each year).
Additional research training and support funding of up to £5,000 per annum is also available.
Please complete application to the GW4 BioMed MRC DTP for an ‘offer of funding’. You may also need to make an 'offer to study' to your chosen institution(s) – further details are on the website. View Website.
Shortlisted applicants for interview will be notified by 19th December.

Related Subjects

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FTE Category A staff submitted: 64.60

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