Grin1 deletion in CRF neurons sex-dependently enhances fear, sociability, and social stress responsivity.

The corticotropin releasing factor (CRF) system plays a critical role in responses to stressful stimuli, and is expressed in many areas of the brain involved in processing fear, anxiety, and social behaviors. To better understand the mechanisms by which the CRF system modulates responses to stressful events and social stimuli, we employed a mouse model that selectively disrupts NMDA receptor function via NMDA receptor subunit NR1 (Grin1) knockout specifically in Cre-expressing CRF neurons. These animals (Cre+/(fGrin1+)) were compared with littermates lacking Cre expression (Cre-/(fGrin1+)).

Paradoxical enhancement of fear expression and extinction deficits in mice resilient to social defeat.

The exposure to stress has been associated with increased depressive and anxiety symptoms, yet not all individuals respond negatively to the experience of stress. Recent rodent social defeat models demonstrate similar individual differences in response to social stress. In particular, mice subjected to chronic social defeat have been characterized as being either "susceptible" or "resilient" by the level of social interaction following social defeat.