ABSTRACT
A deficit in brain serotonin is thought to be associated with deteriorated stress coping behaviour, affective disorders and exaggerated violence. We challenged this hypothesis in mice with a brain-specific serotonin depletion caused by a tryptophan hydroxylase 2 (TPH2) deficiency. We tested TPH2-deficient (Tph2(-/-)) animals in two social situations. As juveniles, Tph2(-/-) mice displayed reduced social contacts, whereas ultrasonic vocalizations (USVs) were unchanged within same-sex same-genotype pairings. Interestingly, juvenile females vocalized more than males across genotypes. Sexually naive adult males were exposed to fresh male or female urine, followed by an interaction with a conspecific, and re-exposed to urine. Although Tph2(-/-) mice showed normal sexual preference, they were hyper-aggressive towards their interaction partners and did not vocalize in response to sexual cues. These results highlight that central serotonin is essential for prosocial behaviour, especially USV production in adulthood, but not for sexual preference.
Subject(s)
Aggression/physiology , Animal Communication , Brain/metabolism , Serotonin/deficiency , Social Behavior , Animals , Behavior, Animal , Female , Male , Mating Preference, Animal/physiology , Mice , Mice, Inbred C57BL , Serotonin/metabolism , Sex Factors , UltrasonicsABSTRACT
Serotonin is a major neurotransmitter in the central nervous system (CNS). Dysregulation of serotonin transmission in the CNS is reported to be related to different psychiatric disorders in humans including depression, impulsive aggression and anxiety disorders. The most frequently prescribed antidepressants and anxiolytics target the serotonergic system. However, these drugs are not effective in 20-30% of cases. The causes of this failure as well as the molecular mechanisms involved in the origin of psychological disorders are poorly understood. Biosynthesis of serotonin in the CNS is initiated by tryptophan hydroxylase 2 (TPH2). In this study, we used Tph2-deficient (Tph2(-/-)) mice to evaluate the impact of serotonin depletion in the brain on mouse behavior. Tph2(-/-) mice exhibited increased depression-like behavior in the forced swim test but not in the tail suspension test. In addition, they showed decreased anxiety-like behavior in three different paradigms: elevated plus maze, marble burying and novelty-suppressed feeding tests. These phenotypes were accompanied by strong aggressiveness observed in the resident-intruder paradigm. Despite carrying only one copy of the gene, heterozygous Tph2(+/-) mice showed only 10% reduction in brain serotonin, which was not sufficient to modulate behavior in the tested paradigms. Our findings provide unequivocal evidence on the pivotal role of central serotonin in anxiety and aggression.
Subject(s)
Aggression/physiology , Anxiety/genetics , Anxiety/physiopathology , Brain/physiopathology , Serotonin/deficiency , Aggression/psychology , Agonistic Behavior/physiology , Animals , Depression/genetics , Depression/physiopathology , Female , Genetic Carrier Screening , Male , Mice , Mice, Inbred C57BL , Phenotype , Serotonin/physiology , Tryptophan Hydroxylase/deficiency , Tryptophan Hydroxylase/geneticsSubject(s)
Endocardium/embryology , Zebrafish/embryology , Animals , Animals, Genetically Modified , Endocardial Cushion Defects/embryology , Endocardial Cushion Defects/genetics , Gene Expression Regulation, Developmental , Green Fluorescent Proteins , Luminescent Proteins/genetics , Mutation , Recombinant Proteins/genetics , Time Factors , Zebrafish/geneticsABSTRACT
Root formation in plants involves the continuous interpretation of positional cues. Physiological studies have linked root formation to auxins. An auxin response element displays a maximum in the Arabidopsis root and we investigate its developmental significance. Auxin response mutants reduce the maximum or its perception, and interfere with distal root patterning. Polar auxin transport mutants affect its localization and distal pattern. Polar auxin transport inhibitors cause dramatic relocalization of the maximum, and associated changes in pattern and polarity. Auxin application and laser ablations correlate root pattern with a maximum adjacent to the vascular bundle. Our data indicate that an auxin maximum at a vascular boundary establishes a distal organizer in the root.
