How Mice Forget to Be Afraid
How Mice Forget to Be Afraid

How Mice Forget to Be Afraid

The animals develop a new memory that overrides the fearful one by inhibiting the cells that encode the original memory.

Kerry Grens
Kerry Grens
May 1, 2020

ABOVE: In the basolateral amygdala of a mouse brain, newly formed fear-extinction memory cells (orange) can override the animal’s past memory of a foot shock.
© XIANGYU ZHAN

EDITOR’S CHOICE IN NEUROSCIENCE

The paper

X. Zhang et al., “Amygdala reward neurons form and store fear extinction memory,” Neuron, 105:1077–93, 2020. 

Fear conditioning, which connects a neutral stimulus with a painful experience in an animal’s brain, can be undone. Put a mouse in a cage where it experienced foot shocks the day before, and its initial response of freezing in place will eventually dissipate once the shock stimulus ceases. While scientists have known about such fear extinction for a long time, they haven’t understood how it happens in the brain.

One hypothesis, says Susumu Tonegawa of MIT, is that a new memory takes the place of the fearful one: the original memory remains intact, but it’s inhibited by the new one. Under certain circumstances, the conditioned fear response can come back, Tonegawa explains. “This suggests the fear is still there, but it is dormant.”

To get to the cellular bottom of this phenomenon, Tonegawa’s team focused on neurons in the murine basolateral amygdala (BLA), a brain area important for fear conditioning. The researchers identified certain neurons that were active during fear extinction and appeared to encode a new memory that suppressed the old fear memory. Using optogenetics, the scientists selectively turned on these Ppp1r1b+ neurons, and the mice quickly extinguished the fear memory in the cage where they had previously received foot shocks. When those neurons were turned off, the animals froze more and exhibited more fear. 

The team also found that Ppp1r1b+ neurons suppressed other BLA neurons, called Rspo2+, that are responsible for the fear memory. Tonegawa says the findings support the idea that Ppp1r1b+ neurons are linked with pleasurable emotions, while Rspo2+ neurons encode negative ones. “This study provides a nice extension on our current models for how the amygdala serves to process positive and negative [emotions],” Kay Tye, a neuroscientist at the Salk Institute for Biological Studies who was not involved in the research, writes in an email to The Scientist