title: Directional theta coherence in prefrontal cortical to amygdalo-hippocampal pathways signals fear extinction.
abstract: Theta oscillations are considered crucial mechanisms in neuronal communication across brain areas, required for consolidation and retrieval of fear memories. One form of inhibitory learning allowing adaptive control of fear memory is extinction, a deficit of which leads to maladaptive fear expression potentially leading to anxiety disorders. Behavioral responses after extinction training are thought to reflect a balance of recall from extinction memory and initial fear memory traces. Therefore, we hypothesized that the initial fear memory circuits impact behavioral fear after extinction, and more specifically, that the dynamics of theta synchrony in these pathways signal the individual fear response. Simultaneous multi-channel local field and unit recordings were obtained from the infralimbic prefrontal cortex, the hippocampal CA1 and the lateral amygdala in mice. Data revealed that the pattern of theta coherence and directionality within and across regions correlated with individual behavioral responses. Upon conditioned freezing, units were phase-locked to synchronized theta oscillations in these pathways, characterizing states of fear memory retrieval. When the conditioned stimulus evoked no fear during extinction recall, theta interactions were directional with prefrontal cortical spike firing leading hippocampal and amygdalar theta oscillations. These results indicate that the directional dynamics of theta-entrained activity across these areas guide changes in appraisal of threatening stimuli during fear memory and extinction retrieval. Given that exposure therapy involves procedures and pathways similar to those during extinction of conditioned fear, one therapeutical extension might be useful that imposes artificial theta activity to prefrontal cortical-amygdalo-hippocampal pathways that mimics the directionality signaling successful extinction recall.
authors.affiliation: Institute of Physiology 1, Westfälische Wilhelms-University, Münster, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Lesting
authors.forename: Thiemo
authors.initials: T
authors.lastname: Daldrup
authors.forename: Venu
authors.initials: V
authors.lastname: Narayanan
authors.forename: Christian
authors.initials: C
authors.lastname: Himpe
authors.forename: Thomas
authors.initials: T
authors.lastname: Seidenbecher
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology; D013826:Theta Rhythm / Q000502:physiology*