+44 (0) 1334462057 jaa7@st-andrews.ac.uk

The main focus of the lab is to try and understand the neural mechanisms that support our ability to remember the things that have happened to us – episodic memory. Most of our work takes a systems neuroscience approach to examine how networks within the hippocampus and entorhinal cortex process memory information.  We use in vivo electrophysiology to examine firing patterns of individual neurons as lab rats carry out memory tasks. We also use molecular and genetic tools to manipulate the network and understand the cellular mechanisms underlying episodic memory.

Complimenting the neuroscientific approach, other lines of research in the lab examine the cognitive mechanisms underlying episodic memory in both human adults and children. Ultimately we aim to apply this work by using our knowledge of mammalian memory networks to help test therapeutic strategies for disorders of memory such as Alzheimer’s disease. Current on-going research projects in the lab include:

 

Role of the Lateral Entrohinal Cortex

 

While it is well known that the hippocampus supports episodic memory in humans and animals our understanding of how the network of structures surrounding the hippocampus contributes to this cognitive function is less well understood. In recent years we have been using in vivo single unit recording and immediate early gene imaging studies combined with molecular and genetic tools to examine the role of one of the main interfaces between the hippocampus and neocortex, the lateral entorhinal cortex (LEC).

Our studies suggest a new role for LEC in associative memory for combinations of features of an event. Trying to remember where you left your keys or where you parked your car? Your LEC will be helping you remember the combination of object and the context in which it was experienced.

Associative memory tasks from Kuruvilla & Ainge 2017

Translating rodent and human memory research

Eye-tracking protocol from Sivakumaran et al. 2018

One very commonly used test of memory in lab rats is the novel object recognition paradigm. This works by making use of rodents’ natural propensity to explore novel objects and assumes that memory for familiar objects supports this novelty seeking behaviour. However, the translation of findings from these rodent studies relies on the assumption that humans and rats use the same memory mechanisms when carrying out this type of task. We are adapting rodent tasks for humans and vice versa to ask whether we are testing the same cognitive processes in both species.

Some of our recent work in humans using eye tracking and standard recognition memory protocols has validated the novel object recognition paradigm by demonstrating it is well correlated with memory sensitivity and not bias.

 

Time vs. context

How do we remember specific events? How is it possible that we can remember hundreds of very similar events that occur in the same location (how many meetings have I had in my office?!)? One way of disambiguating events is to encode the time at which they happened as this is a unique piece of information that can separate each memory from other memories. However, humans are not very good at remembering specific times and dates and as such we rely on other contextual cues that were present during the event (who was there, what the weather was like). Current experiments are asking which neural mechanisms allow is to remember time and contextual information from specific experiences.

Our recent findings call into question the suggestion that context and time are used interchangbly to remember episodes by showing that they can be supported by different retrieval mechanisms.

Episodes presented in different contextual and temporal settings from Persson et al. 2016

Episodic cognition

Vending machine and tokens from the ‘Spoon test’ used in Dickerson et al. 2018

 

It has been suggested that the main function of the episodic memory system is to allow us to mentally travel in time. This allows us to relive things that have happened to us but also allows us to imagine events in the future. If this is the case then we would expect the same systems in the brain to support both episodic memory and episodic future thinking and for these cognitive functions to come online at the same time in development.

Current experiments show that the most commonly used test of future planning in children needs to be treated with caution as 4-year olds performance is strongly influenced by previous positive experience. Results from these studies calls into question the theory that memory and planning rely on the same cognitive mechanisms.

Leptin and episodic memory

 

Recent studies have suggested that irregularities in the system controlling the hormone leptin are linked with Alzheimer’s disease (AD). Leptin levels are reduced in AD patients and leptin has been shown to reduce b-amyloid (Ab) and tau phosphorylation, 2 hallmarks of AD pathology, in animal models of AD. However, we do not know how leptin affects the debilitating cognitive decline in AD which is characterised by deficits in memory, attention, language and spatial orientation in its final stages.

Our recent experiments have shown that leptin upregulates memory mechanisms within the hippocampus and improves episodic memory in mice. On-going studies are examining whether small fragments of the leptin molecule could be a useful therapeutic target for AD.

Increased GluR1 staining in leptin treated neurons from Malekizadeh et al. 2017