The neural mechanisms responsible for sophisticated navigational behavior in rats are currently under intense study for at least two key reasons. First, these mechanisms provide an excellent model for the cognitive processes subserved by the human hippocampus. Second, the location-specific discharge of hippocampal """"""""place cells"""""""" (pyramidal cells of CA3 and CA1) and of related cell types in nearby brains areas suggests the existence of a map-like representation of the environment whose activity is essential for solving difficult spatial problems. To better understand the relationship between behavior and coordinated neuronal discharge in the hippocampal formation, we will record from single cells as rats perform simple tasks. In one study, we will compare changes of cell activity in different areas after environmental changes too subtle to cause, """"""""remapping"""""""" a major change seen when rats are put into a very different, novel environment. As part of the same study, we will investigate a form of pattern completion in CA1 by looking at how discharge in input areas is affected by removing a cue of known salience. We will also ask how accurately changes in goal location choice caused by putting cues into conflict can be predicted from the way the same conflict causes displacements of place cell firing fields. A third experiment arises from an interesting pharmacologic effect that two well-regarded theories make contrary predictions for concerning navigational performance. Thus, dialyzing the GABAA antagonistic picrotoxin into the medial septum increases the precision of place cell firing while greatly reducing the magnitude of hippocampal theta activity. We will therefore ask if precision of goal location choice in a hidden goal task is unchanged or improved, as expected from crisper place cell firing or disrupted as expected from decrements of theta amplitude. Finally, we will continue to record event-specific activity of hippocampal pyramidal cells to test further the idea that these two forms of processing have extremely similar properties despite the strong difference in the kind of information being processed. We hope the proposed work will shed light on the normal operation of a brain structure whose activity is compromised in pathological states including Alzheimer's disease (AD). We also hope that the use of subtle stimulus transformations to cause simpler, more interpretable changes in single cell activity will be a useful new way of analyzing hippocampal function.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Babcock, Debra J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Suny Downstate Medical Center
Schools of Medicine
United States
Zip Code
Lin, Hai; Hangya, Balázs; Fox, Steven E et al. (2012) Repetitive convulsant-induced seizures reduce the number but not precision of hippocampal place cells. J Neurosci 32:4163-78
Barry, Jeremy M; Rivard, Bruno; Fox, Steven E et al. (2012) Inhibition of protein kinase Mýý disrupts the stable spatial discharge of hippocampal place cells in a familiar environment. J Neurosci 32:13753-62
Zynyuk, Larysa; Huxter, John; Muller, Robert U et al. (2012) The presence of a second rat has only subtle effects on the location-specific firing of hippocampal place cells. Hippocampus 22:1405-16
Czurko, Andras; Huxter, John; Li, Yu et al. (2011) Theta phase classification of interneurons in the hippocampal formation of freely moving rats. J Neurosci 31:2938-47
Fenton, Andre A; Lytton, William W; Barry, Jeremy M et al. (2010) Attention-like modulation of hippocampus place cell discharge. J Neurosci 30:4613-25
Hangya, Balázs; Li, Yu; Muller, Robert U et al. (2010) Complementary spatial firing in place cell-interneuron pairs. J Physiol 588:4165-75
Isaac, John T R; Buchanan, Katherine A; Muller, Robert U et al. (2009) Hippocampal place cell firing patterns can induce long-term synaptic plasticity in vitro. J Neurosci 29:6840-50
Lin, Hai; Holmes, Gregory L; Kubie, John L et al. (2009) Recurrent seizures induce a reversible impairment in a spatial hidden goal task. Hippocampus 19:817-27
Lenck-Santini, Pierre-Pascal; Fenton, Andre A; Muller, Robert U (2008) Discharge properties of hippocampal neurons during performance of a jump avoidance task. J Neurosci 28:6773-86
Hok, Vincent; Lenck-Santini, Pierre-Pascal; Roux, Sebastien et al. (2007) Goal-related activity in hippocampal place cells. J Neurosci 27:472-82

Showing the most recent 10 out of 49 publications