Figure 2. Dopamine circuitry in fear-related behaviors.

Dopamine neurons in the ventral tegmental area (VTA) generate signals to encode discrepancy between expected and unexpected outcomes (prediction error). These signals are relayed to several regions that have reciprocal connections with the VTA, such as the amygdala, nucleus accumbens, prefrontal cortex, and hippocampus. These reciprocal connections allow for modification of signals arising from the VTA, leading to precise control of dopamine release within dopamine terminal regions. Within the amygdala, the basolateral amygdala (BLA) encodes CS-US associations, allowing for fear acquisition and retrieval. The BLA projects to the central amygdala (CeA) to generate fear responses and motivated behavior through motor circuitry. Dopamine receptor activity in the amygdala modulates the formation and retrieval of fear associations. Dopamine transmission in the nucleus accumbens core (NAcc Core) is important for encoding the general salience of environmental stimuli, and activity in the nucleus accumbens shell (Nacc Shell) encodes outcome-specific predictions to guide motivated behavior. In the prefrontal cortex, dopamine activity is important for working memory and fear extinction. In the infralimbic region of the prefrontal cortex (IL), dopamine D1 receptors are required for consolidation of fear extinction (Hikind & Maroun, 2008). Activation of D1 receptors in the prelimbic region of the prefrontal cortex (PL) blocks the expression of conditioned fear (Lauzon et al., 2013). Interactions between the hippocampus and VTA are important for relaying contextual information in fear and reward learning. The VTA provides a coordinating signal to generate particular patterns of activity in dopamine terminal regions based on environmental stimuli and prior experience. Dopamine neurons in the substantia nigra are involved in motor responses and project to the dorsal striatum, which selects and alters appropriate behavioral responses based on inputs from a variety of different regions. Together, activity in the substantia nigra, ventral tegmental area, and dopamine terminal regions allow for the generation of appropriate behavioral responses (e.g. freezing, approach, or active avoidance) in response to shifting external stimuli.