Dr Colin Lever
(email at email@example.com)
A few years after my Bachelor's degree at Oxford University, I studed Neuroscience at UCL. I did a Neuroscience MSc, and then a PhD with John O'Keefe (2001) on hippocampal place cells. I stayed in John O’Keefe’s lab as a post-doc working on spatial representation and memory mechanisms, and worked briefly with the Blanchards in USA on anxiety (2005), before setting up my own lab in Leeds University in 2005. I joined the Psychology Dept. in the University of Durham in the summer of 2011. Funders of my research include the Royal Society and BBSRC.
I am a Faculty Member of the Cognitive Neuroscience section of the post-publication peer review service Faculty of 1000.
Current Grant Funding
Biotechnology and Biological Sciences Research Council (BBSRC)
New Investigator Research Grant: BB/G01342X (£394k FEC)
For public lists of my publications, use these author-specific links:
Most of my work has been on understanding the neurobiology of learning and memory. I am particularly interested in the hippocampal formation: its functions, processes, and mechanisms, focusing on memory, spatial cognition, and emotion. The hippocampal formation is typically the first region to degenerate in Alzheimer’s Disease. My lab’s primary technique is to record ensembles of individual neurons and ‘brain waves’ (e.g. the 4-12 Hz theta oscillation) from hippocampal regions, together with behaviour, in freely moving rodents. This can be combined with other manipulations (e.g. injecting amnestic and anxiolytic drugs). We are interested in the interplay between experimental and theoretical work on the hippocampus. Below are some of the specific research areas we are pursuing:
1) Temporal coding and Memory states
We ask questions like: How does the brain know when to encode and when to retrieve? What controls the balance between pattern separation and pattern completion? Tulving and others conjectured that the more novel information is, the longer it will be stored. How might that work? We explore these kinds of questions in the hippocampus, focusing on CA1 place cells (pyramidal cells). Briefly, CA1 can be viewed as having two cortical input streams: one embodying the currently-pertaining sensory environment (entorhinal cortex), and one which is predictive, which makes inferences based on past experience (CA3). Each input stream seems to predominate at different phases of theta, allowing for rapid alternation between encoding and retrieval several times a second. Further, perhaps a novelty-sensitive neuromodulating switch can turn down one input stream relative to the other, dependent on the memory system’s requirement for encoding (bias towards entorhinal input) or retrieving (bias towards CA3 input). It would be adaptive to do this in such a way as to complement the memory state’s plasticity requirements (e.g. LTP for long-term encoding of a novel context, but minimal plasticity in retrieval so old memories aren’t easily corrupted). We showed that, relative to firing in a familiar environment, contextual novelty elicits a later theta phase of firing in CA1 place cells, taking preferred phase closer to the peak of pyramidal-layer theta (Lever et al, 2010). This is interesting because physiological studies show that the balance between long-term potentiation and depression is controlled by theta phase. We interpret our results in terms of a novelty-elicited long-term encoding process. We are currently exploring the mechanisms underlying the later-theta-phase in novelty effect, and functional implications.
2) Boundary Vector cells.
Subsequent to theoretical predictions of ‘boundary vector cells’ (Burgess et al, 2000, Hartley et al, 2000), we actually discovered boundary vector cells (BVCs) in the subiculum of the hippocampal formation (Lever et al, 2009, our first report in Barry et al, 2006). A BVC fires at a preferred distance and compass direction from an environmental boundary. The discovery of BVCs, controlled by external environmental cues, nicely complements the discovery of grid cells, which rely heavily on internal, movement-related input to map space. We are characterising BVCs in more depth, e.g. asking what constitutes a boundary, and how BVCs interact with other fundamental spatial cell types (place cells, head direction cells, grid cells, speed cells) in the service of spatial cognition.
3) The functional associations of hippocampal theta
Septo-hippocampal theta mechanisms crucially subserve the behaviours (navigation, memory, anxiety) thought to depend on the hippocampus: e.g., all anxiolytic drugs reduce reticular-stimulated hippocampal theta frequency, and grid cells in freely moving rats require movement-related input timed by septohippocampal theta. So hippocampal theta seems to reflect both cognitive (e.g. spatial representation) and affective (e.g. arousal/anxiety) variables. In collaboration with Neil Burgess at UCL, we are exploring how spatial representation and anxiolytic drugs act upon two theoretically-distinct theta frequency components.
We are also interested in memory and anxiety in humans, dementia-related research, and in embodied cognition using behavioural economics.
Department of Psychology
Journal papers: academic
- Stewart,S Cacucci,F & Lever,C (2011). Which memory task for my mouse? A systematic review of spatial memory performance in the Tg2576 Alzheimer's mouse model. Journal of Alzheimer's Disease 26(1): 105-126.
- Lever, C , Burton, S Jeewajee, A Wills, TJ Cacucci, F Burgess N & O'Keefe J (2010). Environmental novelty elicits a later theta phase of firing in CA1 but not subiculum. Hippocampus 20(2): 229-234.
- O'Connor,AR, Lever,C & Moulin,CJA (2010). Novel insights into false recollection: A model of déjà vécu. Cognitive Neuropsychiatry 15(1-3): 118-144.
- Lever,C , Burton,S Jeewajee,A O'Keefe,J & Burgess,N (2009). Boundary vector cells in the subiculum of the hippocampal formation. The Journal of Neuroscience 29(31): 9771-9777.
- Wells,CE Krikke,B Saunders,J Whittington,A & Lever,C (2009). Changes to open field surfaces typically used to elicit hippocampal remapping elicit graded exploratory responses. Behavioural Brain Research 197(1): 234-238.
- Lever,C, Jeewajee,A Burton,S, O’Keefe,J & Burgess,N (2009). Hippocampal theta frequency, novelty, and behaviour. Hippocampus 19(4): 409-410.
- Jeewajee,A# Lever,C# , Burton,S O’Keefe,J Burgess,N & (# joint first author) (2008). Environmental novelty is signaled by reduction of the hippocampal theta frequency. Hippocampus 18(4): 340-348.