Impaired extinction of fear and maintained amygdala-hippocampal theta synchrony in a mouse model of temporal lobe epilepsy.
OBJECTIVE
The relationship between epilepsy and fear has received much attention. However, seizure-modulated fear and physiologic or structural correlates have not been examined systematically, and the underlying basics of network levels remain unclear to date. Therefore, this project was set up to characterize the neurophysiologic basis of seizure-related fear and the contribution of the amygdala-hippocampus system.


METHODS
The experimental strategy was composed of the following steps: (1) use of the mouse pilocarpine model of temporal lobe epilepsy (TLE); (2) behavioral analyses of anxiety states in the elevated plus maze test, light-dark avoidance test, and Pavlovian fear conditioning; and (3) probing neurophysiologic activity patterns in amygdala-hippocampal circuits in freely behaving mice.


RESULTS
Our results displayed no significant differences in basic anxiety levels comparing mice that developed spontaneous recurrent seizures (SRS) and controls. Furthermore, conditioned fear memory retrieval was not influenced in SRS mice. However, during fear memory extinction, SRS mice showed an extended freezing behavior and a maintained amygdala-hippocampal theta frequency synchronization compared to controls.


CONCLUSIONS
These results indicate specific alterations in conditioned fear behavior and related neurophysiologic activities in the amygdala-hippocampal network contributing to impaired fear memory extinction in mice with TLE. Clinically, the nonextinguished fear memories may well contribute to the experience of fear in patients with TLE.
Institute for Physiology I, Muenster, Germany.
Jörg
J
Lesting
Matthias
M
Geiger
Rajeevan T
RT
Narayanan
Hans-Christian
HC
Pape
Thomas
T
Seidenbecher
D000161:Acoustic Stimulation; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D003344:Cortical Synchronization; D003463:Cues; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D004597:Electroshock; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology* / Q000523:psychology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000523:psychology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D013826:Theta Rhythm