A thalamo-cortico-amygdala pathway mediates auditory fear conditioning in the intact brain.

The neural substrates of fear conditioning in rats have been well characterized, with converging lines of evidence indicating that conditioned stimulus (CS) and unconditioned stimulus (US) information form a CS-US association in the amygdala. Auditory CS information can reach the amygdala via two routes: a direct thalamo-amygdala pathway, and an indirect thalamo-cortico-amygdala pathway. Although either pathway can fully support learning when the alternate pathway is disrupted, many studies to date have argued that the thalamo-amygdala pathway is the principal auditory CS pathway in intact brains. To test this hypothesis, we trained rats in auditory fear conditioning, and 24 h later lesioned either pathway, leaving the alternate pathway intact. Later, animals were tested for conditioned freezing to the auditory CS. We report that lesions of the thalamo-amygdala pathway produced severe but incomplete deficits in freezing during the tone retention test, while lesions of the thalamo-cortico-amygdala pathway completely abolished freezing during tone presentation. These results suggest that the thalamo-cortico-amygdala pathway is the principal auditory CS pathway when the brain is intact.