Neuronal- and systems-level understanding of spatial and episodic memory.
Lead Research Organisation:
University College London
Department Name: Institute of Neurology
Abstract
Our memories define who we are and the loss of day-to-day (or ?episodic?) memory, for example as a result of Alzheimer?s disease (AD), temporal lobe epilepsy or stroke, has a devastating impact on one?s capacity to live independently and places a huge burden on caregivers and the state.
There is an enormous potential for memory to be improved, both in health and disease, via drugs (which modulate how neurons create and store memories), technological devices and memory strategies. However, our current level of understanding of memory processes means that we are a long way from being able to fully utilize these interventions. Critically, there is a gap between our understanding of memory processes at the level of molecules and cells (the neuronal level) through to the activity of populations of cells throughout the brain (the systems level).
This research is aimed at bridging this gap by providing a detailed understanding of how the actions and interactions of neurons in the brain gives rise to memory. Much of the research focusses on spatial memory, where comparable data can be collected from animals and humans. By pioneering the use of virtual reality to test memory in realistic large-scale environments we have shown that similar neuronal representations are used by humans and animals to find their way around, and that it is possible to understand memory for where things are in terms of the actions of neurons within the brain. Because loss of spatial memory is a prominent and early feature of AD, the findings will be directly relevant to understanding and monitoring the progression of this disease. As well as being a challenge in its own right, understanding the basic neuronal mechanisms by which the brain remembers the spatial context of events, will also have knock-on effects for the progress of medical and therapeutic science. For one example, it can help us to understand how new memories are triggered when a novel event occurs, and how this might go wrong so that memories are lost, and how such loss might be avoided by drugs. For another example, we will test the idea that unwanted intrusive memories in posttraumatic stress disorder occur because the representations of the sights, sounds and feelings associated with a traumatic event have become disconnected with the representations of the specific context in which they occurred.
There is an enormous potential for memory to be improved, both in health and disease, via drugs (which modulate how neurons create and store memories), technological devices and memory strategies. However, our current level of understanding of memory processes means that we are a long way from being able to fully utilize these interventions. Critically, there is a gap between our understanding of memory processes at the level of molecules and cells (the neuronal level) through to the activity of populations of cells throughout the brain (the systems level).
This research is aimed at bridging this gap by providing a detailed understanding of how the actions and interactions of neurons in the brain gives rise to memory. Much of the research focusses on spatial memory, where comparable data can be collected from animals and humans. By pioneering the use of virtual reality to test memory in realistic large-scale environments we have shown that similar neuronal representations are used by humans and animals to find their way around, and that it is possible to understand memory for where things are in terms of the actions of neurons within the brain. Because loss of spatial memory is a prominent and early feature of AD, the findings will be directly relevant to understanding and monitoring the progression of this disease. As well as being a challenge in its own right, understanding the basic neuronal mechanisms by which the brain remembers the spatial context of events, will also have knock-on effects for the progress of medical and therapeutic science. For one example, it can help us to understand how new memories are triggered when a novel event occurs, and how this might go wrong so that memories are lost, and how such loss might be avoided by drugs. For another example, we will test the idea that unwanted intrusive memories in posttraumatic stress disorder occur because the representations of the sights, sounds and feelings associated with a traumatic event have become disconnected with the representations of the specific context in which they occurred.
Technical Summary
Our memories are critical to who we are, and depend on the hippocampal formation (HF) and its interactions with other areas. Damage or dysfunction in this system in dementia, epilepsy, stroke, or posttraumatic stress disorder (PTSD) can cause debilitating mnemonic impairments. The precise neuronal and systems-neuroscience mechanisms supporting memory are unknown, leaving a gap between molecular and physiological knowledge of neurons and synapses and behavioural, structural and electrophysiological measures in human health and disease.
To bridge this gap, I propose a convergent series of behavioural, neuropsychological, functional neuroimaging and electrophysiological experiments in healthy volunteers, neurological patients and behaving rodents, integrated via computational modelling. I will use spatial memory as a model system, using similar tasks in humans and rodents, to begin to understand the neural mechanisms of episodic memory and how they fail in conditions such as dementia and PTSD.
I aim to build a quantitative computational understanding of: i) The neuronal representations underlying memory for environmental spatial locations; ii) The dynamics of these representations, focussing on rhythmicity in the theta band; iii) How novelty affects the neuronal mechanisms of memory, including the creation of new representations; iv) How the mechanisms of spatial memory extend to episodic memory, including the effects of traumatic content or neurological damage.
Proposed research includes: 1) Electrophysiological recording and 2-photon microscopic calcium imaging of the activity of place cells and grid cells in rodents navigating in open environments and in head-fixed virtual reality; 2) Testing my computational model of how place cells and grid cells represent environmental locations, and developing it to include the effects of novelty, development and reconsolidation; 3) Extending the model to human spatial memory and the effects upon it of novelty, neurological damage and Alzheimer?s dementia, using fMRI and studies in neurological patients; 4) Understanding the role of theta-band rhythmicity in neural computation and the coordination of processing across brain regions, using magnetoencephalography in healthy volunteers and intracranial recording in epilepsy patients; 5) Extending the model to include the role of the HF in episodic memory: using fMRI to whether the HF supports recall by providing: attractor dynamics for recall; conjunctive codes for binding together the disparate elements of an event; pre-existing contextual associations for the formation of new memories. 6) Understanding the interaction of the HF with the amygdala and sensory systems in supporting memory for context and content of traumatic /fearful memories, and how this fails in PTSD.
To bridge this gap, I propose a convergent series of behavioural, neuropsychological, functional neuroimaging and electrophysiological experiments in healthy volunteers, neurological patients and behaving rodents, integrated via computational modelling. I will use spatial memory as a model system, using similar tasks in humans and rodents, to begin to understand the neural mechanisms of episodic memory and how they fail in conditions such as dementia and PTSD.
I aim to build a quantitative computational understanding of: i) The neuronal representations underlying memory for environmental spatial locations; ii) The dynamics of these representations, focussing on rhythmicity in the theta band; iii) How novelty affects the neuronal mechanisms of memory, including the creation of new representations; iv) How the mechanisms of spatial memory extend to episodic memory, including the effects of traumatic content or neurological damage.
Proposed research includes: 1) Electrophysiological recording and 2-photon microscopic calcium imaging of the activity of place cells and grid cells in rodents navigating in open environments and in head-fixed virtual reality; 2) Testing my computational model of how place cells and grid cells represent environmental locations, and developing it to include the effects of novelty, development and reconsolidation; 3) Extending the model to human spatial memory and the effects upon it of novelty, neurological damage and Alzheimer?s dementia, using fMRI and studies in neurological patients; 4) Understanding the role of theta-band rhythmicity in neural computation and the coordination of processing across brain regions, using magnetoencephalography in healthy volunteers and intracranial recording in epilepsy patients; 5) Extending the model to include the role of the HF in episodic memory: using fMRI to whether the HF supports recall by providing: attractor dynamics for recall; conjunctive codes for binding together the disparate elements of an event; pre-existing contextual associations for the formation of new memories. 6) Understanding the interaction of the HF with the amygdala and sensory systems in supporting memory for context and content of traumatic /fearful memories, and how this fails in PTSD.
Organisations
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ORCID iD |
| Neil Burgess (Principal Investigator) |