Research Interests
The major research interests of our laboratory are the biological foundations of learning and memory. Although learning and memory are defining features of animal cognition, their implementation in the brain remains far from understood despite many decades of scientific progress. Storage of memory in a retrievable form is critical for well-being and survival. Attainment of reward, avoidance of punishment, execution of skill and social interaction all require these processes. Disturbances resulting from ageing or disease drastically impact quality of life, making learning and memory important processes to understand. Our work is focused on gaining deep insight into the fundamental elements of information storage and retrieval, focusing on cellular and circuit mechanisms that support lasting changes in behavioural responses as a result of sensory experience. In addition, we aim to provide novel insight into aberrant learning and memory in a range of nervous system disorders, with the goal of identifying useful biomarkers of brain dysfunction in these disorders and the potential development of novel treatments. Deeper insight into underlying mechanisms will not only reveal core aspects of how animals including ourselves function, but also has potential to aid education and healthy ageing and inform advances in technology and medicine. Our laboratory is driving for progress in the fundamental understanding of learning and memory (Project 1), but also for translation of our findings into benefit for humans with learning and memory challenges (Project 2). We also strive to implement our understanding of the constraints of learning and memory in education at King's College London (KCL) and beyond (Project 3).
The major research interests of our laboratory are the biological foundations of learning and memory. Although learning and memory are defining features of animal cognition, their implementation in the brain remains far from understood despite many decades of scientific progress. Storage of memory in a retrievable form is critical for well-being and survival. Attainment of reward, avoidance of punishment, execution of skill and social interaction all require these processes. Disturbances resulting from ageing or disease drastically impact quality of life, making learning and memory important processes to understand. Our work is focused on gaining deep insight into the fundamental elements of information storage and retrieval, focusing on cellular and circuit mechanisms that support lasting changes in behavioural responses as a result of sensory experience. In addition, we aim to provide novel insight into aberrant learning and memory in a range of nervous system disorders, with the goal of identifying useful biomarkers of brain dysfunction in these disorders and the potential development of novel treatments. Deeper insight into underlying mechanisms will not only reveal core aspects of how animals including ourselves function, but also has potential to aid education and healthy ageing and inform advances in technology and medicine. Our laboratory is driving for progress in the fundamental understanding of learning and memory (Project 1), but also for translation of our findings into benefit for humans with learning and memory challenges (Project 2). We also strive to implement our understanding of the constraints of learning and memory in education at King's College London (KCL) and beyond (Project 3).
Habituation and Novelty Detection
We primarily work on simple, yet fundamentally important forms of learning and memory that are highly conserved across animal species. This approach allows us to study tractable phenomena in mice, in which a wide range of experimental tools for circuit observation and intervention exist, to gain insight into mechanisms that are likely shared with humans. One such understudied set of processes are collectively known as habituation. Habituation acts as a gateway to higher order cognition, reducing response to stimuli that signal neither reward nor punishment, and enables energy and attention to be assigned to stimuli that bear greater significance or are novel and therefore have the potential to be important. Disrupted habituation is therefore devastating for cognition overall. Habituation is essential to all animals and both humans and mice exhibit it across all sensory modalities and a range of timescales. We use electrophysiology to record activity in thalamo-cortical circuits while mice are habituating, during retrieval of familiarity and detection of novelty and observe dramatic changes in neural responses over seconds, minutes and days as habituation occurs across these timescales. We also experimentally intervene in circuit function by knocking down expression of key factors in specific regions or cell types and by using optogenetics and chemo-genetics to selectively inactivate or activate circuits in a temporally controlled manner. In this way, we are beginning to deeply understand how neural circuits are modified during a foundational form of mammalian memory (See Project 1: Fundamental Insight for more details).
We primarily work on simple, yet fundamentally important forms of learning and memory that are highly conserved across animal species. This approach allows us to study tractable phenomena in mice, in which a wide range of experimental tools for circuit observation and intervention exist, to gain insight into mechanisms that are likely shared with humans. One such understudied set of processes are collectively known as habituation. Habituation acts as a gateway to higher order cognition, reducing response to stimuli that signal neither reward nor punishment, and enables energy and attention to be assigned to stimuli that bear greater significance or are novel and therefore have the potential to be important. Disrupted habituation is therefore devastating for cognition overall. Habituation is essential to all animals and both humans and mice exhibit it across all sensory modalities and a range of timescales. We use electrophysiology to record activity in thalamo-cortical circuits while mice are habituating, during retrieval of familiarity and detection of novelty and observe dramatic changes in neural responses over seconds, minutes and days as habituation occurs across these timescales. We also experimentally intervene in circuit function by knocking down expression of key factors in specific regions or cell types and by using optogenetics and chemo-genetics to selectively inactivate or activate circuits in a temporally controlled manner. In this way, we are beginning to deeply understand how neural circuits are modified during a foundational form of mammalian memory (See Project 1: Fundamental Insight for more details).
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Familiar Stimulus Recognition Assay. Figure adapted from Cooke et al. 2015.
Disorders of Plasticity
Disorders of learning and memory are present throughout the human lifespan. Learning difficulties manifest in a significant number of individuals early in life and there is an evergrowing issue of memory impairments in the elderly as a result of various forms of dementia. Not only do these health issues cause enormous distress and suffering for the individuals affected and their families, but learning and memory conditions in the young and the elderly cause an enormous economic burden on society. If we broaden the scope to consider other forms of plastiticy that occur in the brain, there are also a much wider range of conditions that may effect people at any time of life. Further insight into the constraints and mechanisms of synaptic and neural plasticity, will likely provide new strategies for a range of health issues including recovery from stroke and brain/spinal damage, as well as sensory processing disorders such as tinnitus and migraine. Gaining a deep fundamental understanding of key mechanisms will allow us to eventually target them to promote plasticity where it is diminished and moderate it where it runs wild in this wide range of disorders of the nervous system (See Project 2: Translation for more details).
Disorders of learning and memory are present throughout the human lifespan. Learning difficulties manifest in a significant number of individuals early in life and there is an evergrowing issue of memory impairments in the elderly as a result of various forms of dementia. Not only do these health issues cause enormous distress and suffering for the individuals affected and their families, but learning and memory conditions in the young and the elderly cause an enormous economic burden on society. If we broaden the scope to consider other forms of plastiticy that occur in the brain, there are also a much wider range of conditions that may effect people at any time of life. Further insight into the constraints and mechanisms of synaptic and neural plasticity, will likely provide new strategies for a range of health issues including recovery from stroke and brain/spinal damage, as well as sensory processing disorders such as tinnitus and migraine. Gaining a deep fundamental understanding of key mechanisms will allow us to eventually target them to promote plasticity where it is diminished and moderate it where it runs wild in this wide range of disorders of the nervous system (See Project 2: Translation for more details).
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In this example we have demonstrated a selective deficit in short-term familiarity in a mouse genetic model of Down syndrome. Figure adapted from Morice et al. 2008.
Electroencephalogram (EEG) Biomarkers
The EEG is a relatively easy and affordable way of measuring neural activity non-invasively in humans with fine temporal resolution. Most of this electrophysiological signal is generated by the synchronous activity of cortical excitatory synapses and so it has the potential to provide readouts of synaptic function and dysfunction. Moreover, various rhythms of activity emerge in EEG that are known to reflect the influence of different inhibitory circuit components and these can often be categorized by the frequency of generated oscillations. The EEG is extremely useful in a clinical setting because it may be used as a non-invasive means to measure synaptic, cellular and circuit dysfunction in patients, to stratify these patients into groups that share underlying circuit dysfunction and to measure the response of the brain to candidate treatments. We are currently using mice to understand the underlying cellular and circuit events that occur in the cortex that give rise to the various categorized EEG signals recorded at the skull surface. In addition, we have noted in mice that EEG signal can be reliably influenced by learning and memory retrieval allowing us to constrain the composition of the EEG and understand the origins of this signal more deeply. With this in mind we are particularly interested in gaining a deeper understanding of EEG phenomena related to adaptation and novelty/deviance detection, which are widely used in humans but where the underlying synaptic, circuit and systems level implementation remains poorly understood (See Project 2: Translation for more details).
The EEG is a relatively easy and affordable way of measuring neural activity non-invasively in humans with fine temporal resolution. Most of this electrophysiological signal is generated by the synchronous activity of cortical excitatory synapses and so it has the potential to provide readouts of synaptic function and dysfunction. Moreover, various rhythms of activity emerge in EEG that are known to reflect the influence of different inhibitory circuit components and these can often be categorized by the frequency of generated oscillations. The EEG is extremely useful in a clinical setting because it may be used as a non-invasive means to measure synaptic, cellular and circuit dysfunction in patients, to stratify these patients into groups that share underlying circuit dysfunction and to measure the response of the brain to candidate treatments. We are currently using mice to understand the underlying cellular and circuit events that occur in the cortex that give rise to the various categorized EEG signals recorded at the skull surface. In addition, we have noted in mice that EEG signal can be reliably influenced by learning and memory retrieval allowing us to constrain the composition of the EEG and understand the origins of this signal more deeply. With this in mind we are particularly interested in gaining a deeper understanding of EEG phenomena related to adaptation and novelty/deviance detection, which are widely used in humans but where the underlying synaptic, circuit and systems level implementation remains poorly understood (See Project 2: Translation for more details).
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The frequency composition of local field potential recordings from primary visual cortex is significantly influenced by the familiarity/novelty of the stimulus being viewed. Image adapted from Hayden et al. 2021
Learning to Learn
As well as running a research laboratory we provide extensive teaching for undergraduate and post-graduate students in our roles at King's College London. Universities came into existence not just as educational institutions or for the purposes of research, but to integrate the two together, and this is a major aim of our laboratory. While we run modules on Electrophysiology (The Electrophysiological Brain - Year 2 KCL undergraduate) and Learning and Memory (Memory Mechanisms in Health and Disease - Year 3 KCL undergraduate) we also teach across a wide range of other neuroscience modules at KCL within both undergraduate and master's programs and host research projects within the laboratory across undergraduate, Master's and Doctoral levels. PhD students in the laboratory also have the opportunity to work as graduate teaching assistants on these modules and gain extensive teaching experience themselves. In addition, we are growing a 'Learning to Learn' project not just for university students but also to provide outreach to schools and the wider public. Given that our research focus is the biological constraints and mechanisms of learning and memory it seems natural that we should be able to use this understanding to influence the efficacy and depth of learning in students. One of the major transferrable skills that students acquire in their time at University is how to learn more effectively, as this is often the first time when they are really guiding their own learning. However, it can be a slow and painful process that they never really get on top of. One of our aims is to start imparting these skills earlier, from the moment students arrive at University, and we have even delivered similar teaching sessions to school children before they make the leap to higher education. By framing sessions on strategies to produce deeper and more lasting learning within what we understand about the biology of learning and memory, we hope that students will be better equipped to make the most of their time at University and later in life (See Project 3: Education for more details).
As well as running a research laboratory we provide extensive teaching for undergraduate and post-graduate students in our roles at King's College London. Universities came into existence not just as educational institutions or for the purposes of research, but to integrate the two together, and this is a major aim of our laboratory. While we run modules on Electrophysiology (The Electrophysiological Brain - Year 2 KCL undergraduate) and Learning and Memory (Memory Mechanisms in Health and Disease - Year 3 KCL undergraduate) we also teach across a wide range of other neuroscience modules at KCL within both undergraduate and master's programs and host research projects within the laboratory across undergraduate, Master's and Doctoral levels. PhD students in the laboratory also have the opportunity to work as graduate teaching assistants on these modules and gain extensive teaching experience themselves. In addition, we are growing a 'Learning to Learn' project not just for university students but also to provide outreach to schools and the wider public. Given that our research focus is the biological constraints and mechanisms of learning and memory it seems natural that we should be able to use this understanding to influence the efficacy and depth of learning in students. One of the major transferrable skills that students acquire in their time at University is how to learn more effectively, as this is often the first time when they are really guiding their own learning. However, it can be a slow and painful process that they never really get on top of. One of our aims is to start imparting these skills earlier, from the moment students arrive at University, and we have even delivered similar teaching sessions to school children before they make the leap to higher education. By framing sessions on strategies to produce deeper and more lasting learning within what we understand about the biology of learning and memory, we hope that students will be better equipped to make the most of their time at University and later in life (See Project 3: Education for more details).
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This schematic illustrates the concept of pattern completion, a core property of Hebbian assemblies. By teaching students about the constraints of their own learning they can develop approaches for deep, long lasting memory.