05.2020 | THE SCIENTIST 47© ISTOCK.COM, KEONGDAGREAT; XIANGYU ZHAN
IN THE DARK: Male fruit flies kept in constant darkness forget that their
attempted courtship was rejected.NEUROSCIENCELasting Memories
THE PAPER
S. Inami et al., “Environmental light is required for maintenance of
long-term memory in Drosophila,” J Neurosci, 40:1427–39, 2020.As Earth rotates around its axis, the organisms that inhabit its surface
are exposed to daily cycles of darkness and light. In animals, light has a
powerful influence on sleep, hormone release, and metabolism. Work
by Takaomi Sakai, a neuroscientist at Tokyo Metropolitan University,
and his team suggests that light may also be crucial for forming and
maintaining long-term memories.
The puzzle of how memories persist in the brain has long been of
interest to Sakai. Researchers had previously demonstrated, in both
rodents and flies, that the production of new proteins is necessary
for maintaining long-term memories, but Sakai wondered how this
process persisted over several days given cells’ molecular turnover.
Maybe, he thought, an environmental stimulus, such as the light-dark
cycles, periodically triggered protein production to enable memory
formation and storage.
Sakai and his colleagues conducted a series of experiments to
see how constant darkness would affect the ability of Drosophila
melanogaster to form long-term memories. Male flies exposed to
light after interacting with an unreceptive female showed reduced
courtship behaviors toward new female mates several days later,
indicating they had remembered the initial rejection. Flies kept in
constant darkness, however, continued their attempts to copulate.
The team then probed the molecular mechanisms of these behaviors
and discovered a pathway by which light activates cAMP response
element-binding protein (CREB)—a transcription factor previously
identified as important for forming long-term memories—within certain
neurons found in the mushroom bodies, the memory center in fly brains.
“The fact that light is essential for long-term memory maintenance
is fundamentally interesting,” says Seth Tomchik, a neuroscientist at the
Scripps Research Institute in Florida who wasn’t involved in the study.
However, he adds, “more work will be necessary” to fully characterize
the molecular mechanisms underlying these effects.
—Diana KwonREVERSING FEAR: 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.NEUROSCIENCEFear Extinction
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 Ty e , a neuroscientist at the Salk
Institute for Biological Studies who was not involved in the research,
writes in an email to The Scientist.
—Kerry Grens