Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and a common outcome of war-related brain trauma. However, the mechanisms underlying TLE are not understood. There is evidence from human and animal studies that there are significant alterations in the anatomical connectivity of hippocampal GABAergic interneurons in epileptic brain. However, the functional connectivity and synchronization of identified hippocampal GABAergic interneurons and pyramidal neurons in awake-behaving epileptic animals are not known. Here we propose to use the pilocarpine model of TLE in combination with juxtacellular recording and biocytin labeling, in awake behaving mice navigating on a spherical treadmill, to test the hypothesis that the phase-locked firing of PV+ basket cell and pyramidal neurons is pathologically increased during theta and gamma oscillations but not altered during ripples. We will also test the hypothesis that SOM+ OL-M cells show decreased precision in phase-locking to theta oscillations, no change to gamma oscillations, and increased firing rates during ripples. The experiments of this proposal are designed to specifically target the network mechanisms underlying TLE. It is anticipated that defining the functional consequences of experimental TLE on GABAergic interneurons and pyramidal neurons in the hippocampus will help the future development of better treatments for cognitive dysfunction suffered by patients with TLE. )

Public Health Relevance

) Many patients with temporal lobe epilepsy have impaired short and long-term memory. This impairment in memory may be caused by altered inhibitory circuits in the hippocampus that emerge after insults to the brain. This project will determine whether abnormal firing of inhibitor neurons in the hippocampus contributes to the abnormal functioning of the hippocampus in epileptic model animals. The results may be used in the future to design treatments for memory impairments in patients with epilepsy.)

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01BX001524-01A1
Application #
8333281
Study Section
Neurobiology C (NURC)
Project Start
2012-07-01
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
Indirect Cost
Name
VA Greater Los Angels Healthcare System
Department
Type
DUNS #
066689118
City
Los Angeles
State
CA
Country
United States
Zip Code
90073