Overview

• Dopamine release from specific ventral tegmental area (VTA) neurons signals fear extinction by activating reward-associated neurons in the posterior basolateral amygdala (pBLA).
• Distinct VTA subregions target two amygdala neuron populations: anterior/lateral VTA inputs reinforce fear via Rspo2 neurons in the anterior BLA (aBLA), while central/posterior VTA inputs promote extinction via Ppp1r1b neurons in the pBLA.
• In vivo imaging during fear conditioning and extinction trials showed dopamine activity shifts from fear-encoding Rspo2 neurons to extinction-encoding Ppp1r1b neurons, correlating with reduced freezing behavior.
• Optogenetic manipulation demonstrated causality: inhibiting dopamine inputs to the pBLA impaired extinction, while activating them accelerated it; activating inputs to the aBLA reinstated fear.
• The findings highlight the VTA→pBLA circuit as a promising target for developing treatments for anxiety disorders and PTSD by enhancing fear extinction mechanisms.