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EASTBIO: Unravelling the circuit changes mediating the development of episodic memory


About This PhD Project

Project Description

Episodic memory in humans emerges relatively late during juvenile development in comparison to other forms of memory, and is particularly vulnerable to disruption in normal ageing, as well as in neurodevelopmental and neurodegenerative diseases. We have recently found that the ability of rats to show memory in an episodic-like object-place-context (OPC) recognition task also emerges late in juvenile development (Asiminas et al, 2019) compared to non-episodic memory tasks. The aim of the PhD project is to identify the circuit changes that mediate the late emergence of episodic memory. The OPC task is known to depend on the integrity of the hippocampus (Langston & Wood, 2010), as well as the lateral entorhinal cortex and medial prefrontal cortex. In this PhD project the student will utilise a combination of behavioural and in vivo electrophysiological recording techniques to characterise the key changes in this circuitry that mediate the emergence of episodic memory in juvenile rats. A second part of the project will be to use a “reverse translation” approach whereby the student will use a behavioural task that has been designed to mimic the OPC task used in the rat studies, to test children of different ages to determine how episodic memory ability develops. Using this approach will enable us to understand more closely how the findings in rats relate to the development of episodic memory abilities in children, allowing for more translational research in the future.

The student will be trained and gain experience in a wide repertoire of techniques including: 1. Rat stereotaxic surgery to implant microdrives containing recording tetrodes into multiple brain regions in juveniles and adults. 2. In vivo tetrode recording from freely behaving rats, together with spike sorting using cluster cutting software followed by analysis of the spatial firing properties of individual cells, ensemble analyses and local field potential analyses. 3. Behavioural testing in tasks, designed to assess episodic memory in rats, together with analysis of video and tracking data for various measures of behavioural performance. 4. Cognitive testing using screen based tasks and eye tracking in human subjects. 5. Experimental design and statistics, as well as training in the responsible use of animals in bioscience research (BBSRC guidelines), and the ARRIVE guidelines for the reporting of in vivo experiments.

The rodent experiments will be conducted in Edinburgh, with input from all three supervisors who have overlapping and complementary expertise. Specifically, behavioural testing techniques for juvenile and adult rats are routinely used in both the Wood and Langston labs. The in vivo electrophysiological recording techniques are routinely used in the Wood and Dudchenko labs, primarily in adult rats, while the Langston lab has considerable experience in conducting surgery and behaviour in juvenile rats. The human experiments will be conducted in Dundee and Stirling, where the Langston and Dudchenko labs have been developing a version of the OPC task for testing children.

References:
Langston & Wood (2010) Hippocampus 20(10):1139-53.
Langston, Ainge, Couey, Canto, Bjerknes, Witter, Moser & Moser (2010) Science 328(5985):1576-80
Harland, Grieves, Bett, Stentiford, Wood & Dudchenko (2017) Current Biology 27(17):2706-2712.

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