title: Social defeat: impact on fear extinction and amygdala-prefrontal cortical theta synchrony in 5-HTT deficient mice.
abstract: Emotions, such as fear and anxiety, can be modulated by both environmental and genetic factors. One genetic factor is for example the genetically encoded variation of the serotonin transporter (5-HTT) expression. In this context, the 5-HTT plays a key role in the regulation of central 5-HT neurotransmission, which is critically involved in the physiological regulation of emotions including fear and anxiety. However, a systematic study which examines the combined influence of environmental and genetic factors on fear-related behavior and the underlying neurophysiological basis is missing. Therefore, in this study we used the 5-HTT-deficient mouse model for studying emotional dysregulation to evaluate consequences of genotype specific disruption of 5-HTT function and repeated social defeat for fear-related behaviors and corresponding neurophysiological activities in the lateral amygdala (LA) and infralimbic region of the medial prefrontal cortex (mPFC) in male 5-HTT wild-type (+/+), homo- (-/-) and heterozygous (+/-) mice. Naive males and experienced losers (generated in a resident-intruder paradigm) of all three genotypes, unilaterally equipped with recording electrodes in LA and mPFC, underwent a Pavlovian fear conditioning. Fear memory and extinction of conditioned fear was examined while recording neuronal activity simultaneously with fear-related behavior. Compared to naive 5-HTT+/+ and +/- mice, 5-HTT-/- mice showed impaired recall of extinction. In addition, 5-HTT-/- and +/- experienced losers showed delayed extinction learning and impaired recall of extinction. Impaired behavioral responses were accompanied by increased theta synchronization between the LA and mPFC during extinction learning in 5-HTT-/- and +/- losers. Furthermore, impaired extinction recall was accompanied with increased theta synchronization in 5-HTT-/- naive and in 5-HTT-/- and +/- loser mice. In conclusion, extinction learning and memory of conditioned fear can be modulated by both the 5-HTT gene activity and social experiences in adulthood, accompanied by corresponding alterations of the theta activity in the amygdala-prefrontal cortex network.
authors.affiliation: Institute of Physiology I, Westfälische Wilhelms-University, Münster, Germany.
authors.forename: Venu
authors.initials: V
authors.lastname: Narayanan
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heiming
authors.forename: Friederike
authors.initials: F
authors.lastname: Jansen
authors.forename: Jörg
authors.initials: J
authors.lastname: Lesting
authors.forename: Norbert
authors.initials: N
authors.lastname: Sachser
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.forename: Thomas
authors.initials: T
authors.lastname: Seidenbecher
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003344:Cortical Synchronization / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D005838:Genotype; D008297:Male; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency* / Q000378:metabolism; D012919:Social Behavior
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins