Neurobiology: Novel peptide pathways impact threat discrimination

Abstract

Discriminating dangerous predictive stimuli from non-threatening stimuli is vital for maintaining optimal behavioral strategies. A new study finds that novel stress-related peptide pathways to the dopaminergic midbrain play a fundamental role in threat generalization.

Figure 1.. Novel dynorphin inputs to VTA dopamine neurons regulate threat discrimination and anxiety-like behavior.

Associative memories guide the behavioral response to previously encountered stimuli. Behavioral discrimination between cues that were paired with shock and cues that were not shock-predictive follows an inverted U-shaped pattern, with optimal discrimination at moderate threat intensities and generalization at high intensities. Fellinger et al demonstrate that threat generalization requires dynorphin signaling at kappa opioid receptors in the ventral tegmental area (VTA). Tracing studies revealed previously unidentified dynorphin inputs to the VTA from the bed nucleus of the stria terminalis (BNST) and the dorsal raphe (DRN). Activating either of these dynorphin projections is sufficient to induce anxiety-like behavior; however, only activation of the DRN projection promotes threat generalization.