PhD Studentship: Using Genetic Tools to Unravel the Cellular Circuitry of the Subiculum

University of Exeter - College of Life and Environmental Sciences

The South West Biosciences Doctoral Training Partnership (SWBio DTP) is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bristol, Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence. The partnership has a strong track record in advancing knowledge through high quality research and teaching in partnership with industry and government.

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP). Up to 4 fully-funded studentships are being offered to start in September 2018 at the University of Exeter.

Main supervisor: Dr Mick Craig
Co-supervisor: Dr John Aggleton
Co-supervisor: Dr Jon Brown

Project:

One of the most widely-studied structures in the brain is the hippocampal formation, due to its essential role in cognitive functions such as memory and spatial navigation, and involvement in myriad neurological conditions such as epilepsy and dementia. The hippocampus proper consists of a single layer of excitatory neurons surrounded by other layers that receive inputs from various regions and contain a number of inhibitory interneurons. Most researchers in the hippocampal field focus on the hippocampus proper and the entorhinal cortex, with the latter both providing input to, and receiving output from the former. However, between the hippocampus proper and entorhinal cortex lie a number of other regions with functions that are still poorly-defined. The aim of this project is to study the function of one such region, the subiculum.

The subiculum is one of the main ‘gateways’ for information flowing out of the hippocampus. The presence of spatially-tuned neurons in the subiculum implies that some degree of information-processing must occur in this region. However, the lack of a clear laminar structure or easily-identifiable subtypes of principal cells in the subiculum makes this region difficult to study in comparison with other areas in the hippocampal formation. Fortunately, two Cre driver mouse lines have recently been created that allow the selectively targeting of subsets of excitatory pyramidal cells in the subiculum. The successful student will use a combination of behavioural experiments and both in vitro and in vivo electrophysiology to study how these two populations of pyramidal cells contribute to the function of the subiculum.

To determine whether these pyramidal cell subtypes differ in their projections, the student will express excitatory optogenetic tools such as channelrhodopsin in each subtype and map the projections from these neurons to other structures by making patch clamp recordings using in vitro brain slices. By expressing an inhibitory opsin such as ArchT and inactivating the pyramidal cell subtypes while a mouse navigates a maze, the student will use in vivo electrophysiological recordings to determine whether either of these pyramidal cell subtypes contribute to the spatial tuning of subicular neurons.

This method will also allow the student to determine whether either of these pyramidal cell subtypes contributes to spatial memory, which will be tested through tasks such as rewarded alternation on a T maze. Overall, this project provides an exciting opportunity for a student to gain interdisciplinary skills in electrophysiology and behavioural neuroscience, and to contribute important knowledge about a crucial, but understudied, part of the brain.

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Type / Role:

PhD

Location(s):

South West England