Previously we have found that activating Thy1 neurons, a subset of glutamatergic neurons in the basolateral amygdala (BLA), prevented fear learning and enhanced fear extinction in mice. These findings suggest that the activation of BLA Thy1 neurons promotes fear inhibition. To continue behaviorally characterizing the effects of activating these neurons, we evaluated their influence on social interaction following social defeat stress. Thy1 neurons were virally transduced to express a designer receptor exclusively activated by a designer drug (DREADD). This chemogenetic approach permits selective activation of BLA Thy1 neurons through peripheral administration of the designer drug, clozapine N-Oxide (CNO).Three weeks after they were infused with the virus coding for the activational DREADD rM3D, mice were subjected to social defeat stress for two consecutive days. Testing took place 24 hours after the final defeat. Thirty minutes prior to the test for social interaction, all mice were injected with CNO to activate BLA Thy1 neurons expressing rM3D. Activation of Thy1 neurons in the BLA increased social interaction during testing in defeated mice compared to control-defeated mice. These data suggest that Thy1 neuron activation within the BLA promotes fear inhibition. In future experiments we will examine brain regions downstream of BLA Thy1 neurons, to map out the circuitry involved in fear inhibition.
Dr. Aaron M Jasnow
Dr. T Lee Gilman
Previously we have found that activating Thy1 neurons in the basolateral amygdala (BLA) prevented fear learning and enhanced fear extinction in mice, suggesting these neurons promote fear inhibition. To continue behaviorally investigating this effect, we evaluated the influence of Thy1 neuron activation on social interaction following social defeat stress. Thy1 neurons were infused with a virus that allows for selective activation by clozapine N-oxide (CNO). Mice were subjected to social defeat stress, then 24 hours later injected with CNO to activate BLA Thy1 neurons prior to a social interaction test. This BLA-specific Thy1 neuron activation increased social interaction during testing in defeated mice compared to non-activated controls. These data support a role of BLA Thy1 neuron activation in promoting fear inhibition in a social context.