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Updated: May 11, 2026
Optogenetic Manipulation of Neuronal Activity to Modulate Behavior in Freely Moving Mice
Published on: October 27, 2020
Suppression of serotonin neuron firing increases aggression in mice
Enrica Audero1, Boris Mlinar, Gilda Baccini
1Mouse Biology Unit, European Molecular Biology Laboratory, 00015 Monterotondo, Italy.
Abstract:
Numerous studies link decreased serotonin metabolites with increased impulsive and aggressive traits. However, although pharmacological depletion of serotonin is associated with increased aggression, interventions aimed at directly decreasing serotonin neuron activity have supported the opposite association. Furthermore, it is not clear if altered serotonin activity during development may contribute to some of the observed associations. Here, we used two pharmacogenetic approaches in transgenic mice to selectively and reversibly reduce the firing of serotonin neurons in behaving animals. Conditional overexpression of the serotonin 1A receptor (Htr1a) in serotonin neurons showed that a chronic reduction in serotonin neuron firing was associated with heightened aggression. Overexpression of Htr1a in adulthood, but not during development, was sufficient to increase aggression. Rapid suppression of serotonin neuron firing by agonist treatment of mice expressing Htr1a exclusively in serotonin neurons also led to increased aggression. These data confirm a role of serotonin activity in setting thresholds for aggressive behavior and support a direct association between low levels of serotonin homeostasis and increased aggression.
Insights
Decreased serotonin neuron activity, particularly in adulthood, is linked to increased aggression in mice. This challenges previous assumptions about serotonin
Area of Science:
- Neuroscience
- Behavioral Science
- Pharmacology
Background:
- Existing research suggests a link between lower serotonin levels and increased aggression.
- However, studies on directly reducing serotonin neuron activity have yielded conflicting results.
- The role of developmental serotonin activity in aggression remains unclear.
Purpose of the Study:
- To investigate the causal relationship between serotonin neuron activity and aggression using pharmacogenetic mouse models.
- To determine if reducing serotonin neuron firing impacts aggressive behavior.
- To explore the developmental timing of serotonin's influence on aggression.
Main Methods:
- Utilized two pharmacogenetic approaches in transgenic mice to selectively and reversibly reduce serotonin neuron firing.
- Investigated the effects of conditional serotonin 1A receptor (Htr1a) overexpression in serotonin neurons.
- Administered agonist treatment to suppress serotonin neuron firing in specific mouse lines.
Main Results:
- Chronic reduction in serotonin neuron firing was associated with heightened aggression.
- Overexpression of Htr1a in adulthood, but not during development, increased aggression.
- Rapid suppression of serotonin neuron firing also led to increased aggression.
Conclusions:
- Serotonin activity plays a critical role in regulating aggression thresholds.
- Low serotonin homeostasis is directly associated with increased aggressive behavior.
- The timing of altered serotonin activity (adulthood vs. development) influences its effect on aggression.
