The main objective of research in our laboratory is to describe neuronal mechanisms of long-term memory storage at the systems level and to investigate how coordinated neuronal activity and synaptic plasticity in distributed cell assemblies can result in the formation of new cell assemblies. In addition, we are interested in the translational implications of this basic research and in understanding whether the neurodegenerative processes underlying dementia can result from a failure to appropriately organize neuronal activity and synaptic plasticity during our adult lives.
This is addressed by recording from many single neurons (up to 100) in the brain simultaneously and by testing how their activity is coordinated before, during, and long after learning. The recording methods are complemented by computational and analytical approaches, and also by molecular techniques that allow us to manipulate the activity of neuronal networks and to test whether the identified mechanisms are necessary for memory formation. Using these methods, we previously discovered neuronal network mechanisms that combine spatial and nonspatial information in the mammalian hippocampus, and showed that orthogonal encoding of the two types of information is used to generate very different neuronal firing patterns for very similar sensory input. Such pattern separation is thought to be a prerequisite for storing a large number of separate memories. To test this hypothesis, we currently investigate how multiple memories are encoded in the hippocampus as well as in a more widely distributed cortical network.
In complementary research program, we aim to investigate how memory processing is altered in the aged brain and when the brain is affected by neurodegenerative disorders. Since memory processing first appears relatively intact in degenerating neuronal networks, but then catastrophically fails, we aim to determine in which way and to what extent a cell assembly can be degraded before failing to support memory retrieval.
Koenig J, Linder AN, Leutgeb JK, Leutgeb S. The spatial periodicity of grid cells is not sustained during reduced theta oscillations. Science 332, 592-595. Download reprint.
Colgin LL*, Leutgeb S*, Jezek K, Leutgeb JK, Moser EI, McNaughton BL, Moser MB (2010). Attractor-map versus autoassociation based attractor dynamics in the hippocampal network. J. Neurophysiol. 104, 35-50. *These authors contributed equally.
Alme CB, Buzzetti RA, Marrone DF, Leutgeb JK, Chawla MK, Schaner MJ, Bohanick JD, Khoboko T, Leutgeb S, Moser EI, Moser MB, McNaughton BL, Barnes CA. Hippocampal granule cells opt for early retirement. Hippocampus 20, 1109-1123.
Kjelstrup KB, Solstad T, Brun VH, Hafting T, Leutgeb S, Witter MP, Moser EI, Moser MB (2008). Finite scale of spatial representation in the hippocampus. Science 321, 140-143.
Leutgeb S (2008). Neuroscience. Detailed differences. Science 319, 1623-1624.
Brun VH, Leutgeb S, Wu H-Q, Schwarcz R, Witter MP, Moser EI and Moser M-B (2008). Impaired spatial representation in CA1 after lesion of direct input from entorhinal cortex. Neuron 57, 290-302.
Leutgeb S, Leutgeb JK (2007). Pattern separation, pattern completion, and new neuronal codes in a continuous CA3 map. Learn. Mem. 14, 745-757.
Leutgeb JK, Leutgeb S, Moser M-B, Moser EI (2007). Distinct mechanisms for pattern separation in dentate gyrus and CA3 of the hippocampal formation. Science 315, 961-966.
Leutgeb S, Leutgeb JK, Moser EI, Moser M-B (2006). Fast rate coding in hippocampal CA3 cell ensembles. Hippocampus 16, 765-774.
Leutgeb S, Leutgeb JK, Moser M-B, Moser EI (2005). Place cells, spatial maps and the population code for memory. Curr. Opin. Neurobiol. 15, 738-746.
Leutgeb S, Leutgeb JK, Barnes CA, Moser EI, McNaughton BL, Moser M-B (2005). Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science 309, 619-623.
Stefan Leutgeb is a new faculty member at U.C. San Diego.