Shift in fear retrieval circuitry eyed in anxiety disorders – NIH-funded studies
January 21, 2015 • Press Release
People with anxiety disorders, such as post traumatic stress disorder (PTSD), often experience prolonged and exaggerated fearfulness. Now, an animal study suggests that this might involve disruption of a gradual shifting of brain circuitry for retrieving fear memories…Immediately after fear conditioning, a circuit running from the prefrontal cortex, the executive hub, to part of the amygdala, the fear hub, was engaged to retrieve the memory. But several days later…retrieval had migrated to a different circuit – from the prefrontal cortex to an area in the thalamus, called the paraventricular region (PVT). The PVT, in turn, communicates with a different central part of the amygdala that orchestrates fear learning and expression.
The researchers say that the PVT may serve to integrate fear with other adaptive responses, such as stress, thereby strengthening the fear memory…“In people with anxiety disorders, any disruption of timing-dependent regulation in retrieval circuits might worsen fear responses occurring long after a traumatic event,”…they showed conclusively that neurons originating in the PVT regulate fear processing by acting on a class of neurons that store fear memories in the central amygdala area.
The Li team traced this activity in the PVT to the action of a messenger chemical, brain-derived neurotrophic factor (BDNF), which has previously been implicated in mood and anxiety disorders. For example, altered BDNF expression has been linked to PTSD.
BDNF from the PVT, working via a specific receptor, activated the memory-storing amygdala neurons. Simply infusing BDNF into the central amygdala area caused mice to freeze in fear, suggesting that it not only enables the formation of fear memories, but also the expression of fear responses.
Although rats’ behavior did not change over time following fear conditioning, the underlying circuitry activated to retrieve the fear memory shifted, perhaps increasing its staying power. An initial circuit from the pre-limbic prefrontal cortex (PL) to the basolateral amygdala (BLA) was supplanted, a week later, by a circuit to the central amygdala (CeA) via the paraventricular nucleus of the thalamus (PVT). It’s thought that the PVT may serve to integrate fear with other adaptive responses. The discovery may provide clues to improved treatments for anxiety disorders.