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Jill Leutgeb

Research

Episodic memories are unique in that they contain information about what happened when and where. Although these memories are formed rapidly and occur only once they can be distinguished from many similar memories even though only few of the features of which they are composed are distinct. The hippocampus is essential for the encoding of episodic memories and has been modeled to perform this function by mediating the convergence of multiple representations of upstream cortical areas into a single, unique memory trace. Our lab is interested in understanding how the hippocampus performs this operation, as well as how the neuronal networks of this brain region combine information about what happened when and where to establish a lasting memory.

The main goal of our research is to describe the neural basis of memory formation and retrieval at the systems level, and to determine how the various subregions of the medial temporal lobe, including the hippocampus, contribute to memory processing. We are interested in what type of information the distinct populations of medial temporal lobe neurons convey and how coordinated neuronal activity and synaptic plasticity in these networks contribute to the distinct computations essential for the encoding of episodic memory.

Our lab is particularly interested in understanding the network computations of neuronal populations in the first processing stages of the hippocampus, namely the CA3 and dentate gyrus. The anatomically distinct arrangement of this brain region has inspired many computational models that have hypothesized their distinct roles in memory formation. While behavioral studies have supported many of these predictions, very little is known about how the neural networks in the CA3-dentate network perform these functions, and what contribution the various cell populations within the network contribute to the encoding necessary for memory formation.

To address these questions we record simultaneously from large groups of neurons (up to 100) in anatomically and functionally related circuits in the mammalian brain during learning. Our lab combines high-density electrophysiology, behavioral testing, theoretical modeling, and pharmacological and molecular manipulations as a multidisciplinary approach to understanding the neural basis of cognition.

Understanding the contribution of the various cell populations within the CA3-dentate network to memory formation will have considerable importance for systems neuroscience and also for translational research since the dentate gyrus is among the first structures in the brain to show decreased neuronal activity in Alzheimer’s disease. In addition, diverse changes in the dentate network and the activity patterns of its neurons have also been linked to the onset of temporal lobe epilepsy. We are interested in understanding how the structural reorganization of memory circuits during disease impairs their contribution to memory and results in the profound memory impairments reported in medial temporal lobe epilepsy. The various phases of MTL epilepsy are associated with distinct memory impairments, and we seek to determine their underlying network mechanisms.

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Publications

  • Mankin EA, Sparks FT, Slayyeh B, Sutherland RJ, Leutgeb S, Leutgeb JK (2012) A neuronal code for extended time in the hippocampus. PNAS, 109:19462-19467.
  • Koenig J, Linder AN, Leutgeb JK, Leutgeb S (2011) The spatial periodicity of grid cells in not sustained during reduced theta oscillations. Science 332:592-595.
  • Leutgeb JK, Leutgeb S (2010) The dentate gyrus: a comprehensive guide to structure, function, and clinical implications. Hippocampus online ahead of press, DOI: 10.1002/hipo.20662.
  • 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 (2010) Hippocampal granule cells opt for early retirement. Hippocampus 20:1109-1123.
  • 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.
  • Leutgeb JK, Leutgeb S, Moser M-B, Moser EI (2007) Pattern separation in dentate gyrus and CA3 of the hippocampus. Science 315:961-966.
  • Leutgeb JK, Moser EI (2007) Enigmas of the dentate gyrus. Neuron 55:176-178.
  • Leutgeb S, Leutgeb JK (2007) Pattern separation, pattern completion and new neuronal codes within a continuous CA3 map. Learn. Mem. 14:745-757.
  • Leutgeb S, Leutgeb JK, Moser EI, Moser M-B (2006) Fast rate coding in hippocampal CA3 cell assemblies. Hippocampus 16:765-774.
  • Leutgeb JK, Leutgeb S, Treves A, Meyer R, Barnes CA, McNaughton BL, Moser
  • M-B, Moser EI (2005) Progressive transformation of hippocampal neuronal representations in "morphed" environments. Neuron 48:345-358.
  • 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.
  • Leutgeb S, Leutgeb JK, Treves A, Moser M-B, Moser EI (2004) Distinct ensemble codes in hippocampal areas CA3 and CA1. Science 305:1295-1298.