UCLA

Fear and defensive behaviors are regulated by complex interactions among many different brain regions. Pathways for individual responses to fear such as freezing and startle potentiation have been well defined, but mechanisms for selecting between competing defensive responses are not fully understood. Research presented here has focused on elucidating the neural mechanisms modulating defensive responding. Pharmacological experiments investigating how neuromodulatory signaling in the periaqueductal gray (PAG) mediates conditional and unconditional responses to aversive stimuli showed that mu-opioid receptors may selectively regulate descending supraspinal motor pathways that drive active movement behaviors. Additional pharmacological experiments investigated the role of medial prefrontal cortex (mPFC) in defensive action selection. Results suggested that mPFC might bidirectionally modulate active defensive responding. Electrophysiological recording experiments identified individual cell populations in areas of mPFC that seem to mediate conditional freezing and flight, indicative of a more diverse role for mPFC in regulating defensive expression than other past studies have shown. Finally, behavioral experiments examining the nature of fear reinstatement showed for the first time that defensive freezing can be reinstated by a "reminder" stimulus rather than an aversive event. Findings presented here provide evidence for a novel, hypothetical model of how fear and defensive behaviors are mediated by neural circuits in the amygdala (AMG), PAG, mPFC.