Notch developmental pathway regulates fear memory formation

August 07, 2014

Nature is thrifty. The same signals that embryonic cells use to decide whether to become nerves, skin or bone come into play again when adult animals are learning whether to become afraid.

Researchers at Yerkes National Primate Research Center, Emory University, have learned that the molecule Notch, critical in many processes during embryonic development, is also involved in fear memory formation. Understanding fear memory formation is critical to developing more effective treatments and preventions for anxiety disorders such as post-traumatic stress disorder (PTSD).

The results are scheduled for publication online this week by the journal Neuron.

"We are finding that developmental pathways that appear to be quiescent during adulthood are transiently reactivated to allow new memory formation to occur," says Kerry Ressler, MD, PhD, professor of psychiatry and behavioral sciences at Emory University School of Medicine and Yerkes National Primate Research Center, and senior author of the paper.

The first author of the paper is postdoctoral fellow Brian Dias, PhD, and co-authors include undergraduates Jared Goodman, Ranbir Ahluwalia and Audrey Easton, and post-doctoral researcher Raul Andero, PhD.

The Notch signaling pathway, present in insects, worms and vertebrates, is involved in embryonic patterning as well as nervous system and cardiovascular development. It's a way for cells to communicate and coordinate which cells are going to become what types of tissues.

Dias and Ressler probed the Notch pathway because they were examining many genes that are activated in the brains of mice after they learn to become afraid of a sound paired with a mild foot-shock. They were looking for changes in the amygdala, a region of the brain known to regulate fear learning.

The researchers were particularly interested in micro RNAs. MicroRNAs do not encode proteins but can inhibit other genes, often several at once in a coordinated way. Dias and Ressler found that levels of miRNA-34a are increased in the amygdala after fear learning occurs. A day after fear training, animals whose brains were injected with a virus engineered to carry a "sponge" against miRNA-34a froze less often than control animals.

The researchers found that miRNA-34a regulated several genes that encode components of the Notch pathway. They believe their study is the first to link miRNA-34a and Notch signaling to a role in memory consolidation.

Notch is under investigation as a target in the treatment of various cancers and some drugs that target Notch have been well-tolerated by humans.

"From a therapeutic perspective, our data suggest that relevant drugs that regulate Notch signaling could potentially be a starting point for preventing or treating PTSD," Dias says.
-end-


Emory Health Sciences

Related Embryonic Development Articles from Brightsurf:

Unraveling a mystery surrounding embryonic cells
Last year, researchers at the University of California, Riverside, identified the early origins of neural crest cells -- embryonic cells in vertebrates that travel throughout the body and generate many cell types -- in chick embryos.

Organoids produce embryonic heart
Bioengineers at EPFL have used organoids - tiny lab-grown organs - to mimic the early development of the heart in the mouse embryo.

Embryonic heart development: Unprecedented insight from 4D OCT
Thanks to innovations in light-based technology, fresh insights are now available into the biomechanics of mammalian cardiogenesis--and in particular, the pumping dynamics of the mammalian tubular embryonic heart.

CNIC researchers discover a system essential for limb formation during embryonic development
Scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have identified a system that tells embryonic cells where they are in a developing organ

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

Disruption of glycine receptors to study embryonic development and brain function
Researchers from Max Planck Florida Institute for Neuroscience, University of Toyama, Yamagata University, Cairo University, RIKEN Center for Integrative Medical Sciences and Setsunan University joined forces to further study glycine receptors, particularly glycine receptor alpha-4 (Glra4), during development.

Unlocking the black box of embryonic development
Little is known about the molecular and cellular events that occur during early embryonic development in primate species.

Signaling waves determine embryonic fates
Embryonic stem cells begin to self-organize when they sense interacting waves of molecular signals that help them start -- and stop -- differentiating into patterns.

Shocking embryonic limbs into shape
In a new study published in EPJ E, Vincent Fleury and Ameya Vaishnavi Murukutla from Universite Paris Diderot, Paris, France use the stimulation of chicken embryos with electric shocks to propose a mechanism for vertebrate limb formation.

Using an embryonic pause to save the date
A date palm seedling can pause its development to boost its resilience before emerging into the harsh desert environment.

Read More: Embryonic Development News and Embryonic Development Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.