Nav: Home

Optimized sensors to study learning and memory

March 09, 2017

Learning and memory are crucial aspects of everyday life. When we learn, our neurons use chemical and molecular signals to change their shapes and strengthen connections between neurons, a process known as synaptic plasticity. In Ryohei Yasuda's lab at Max Planck Florida Institute for Neuroscience (MPFI), scientists are working to understand how these molecules send messages throughout the neuron. To achieve this, his team is constantly working to develop high-resolution imaging techniques to visualize the activity and location of the molecules involved in the process. Ada Tang, Ph.D., a postdoctoral researcher in Yasuda's lab, developed new molecular biosensors, which helped her visualize the activity of two signaling proteins crucial to synaptic plasticity, ERK and PKA. These proteins send messages to other proteins by adding a phosphate group to the target proteins. The team found that these proteins, which were already known to play a role in synaptic plasticity, learning, and memory, have surprising properties in their activity. The work was published in March 2017 in Neuron.

Dendrites are thin extensions that come out of a neuron's cell body and receive messages from other neurons. They branch out to form a tree-like structure, each branch typically extending tens of micrometers. They are covered by spines: tiny protrusions that receive inputs from other neurons and initiate molecular signals inside the cell. When a spine is strongly stimulated, it grows and strengthens to encode memories. Scientists have previously used traditional pharmacological methods such as western blotting to determine the activity of ERK and PKA averaged over many cells, but they haven't been able to visualize the molecules directly in dendritic spines because of their small size.

To design sensors sensitive enough to visualize these molecules, Tang created a new dye molecule, sREAChet, a modified dark but light-absorbing molecule. When she linked sREAChet with both green fluorescent protein (GFP) and a target peptide of the protein, she found that it could readout the activity of the protein with 2-3 times higher sensitivity compared to previous sensors. This made the sensitivity sufficient for imaging activity in single dendritic spines. "These sensors will be useful for researchers in a broad field of cell biology since ERK and PKA are involved in a variety of phenomena in cells and their abnormal activity is related to many diseases including cancer and mental diseases," explained Yasuda.

To demonstrate the usefulness of the new sensors, Yasuda's team first stimulated individual dendritic spines, then used a special microscope called a 2-photon fluorescence lifetime microscope to visualize how ERK and PKA activity moves from a single spine. To their surprise, the team found the proteins' activity did not stay within the individual spine, but spread much more than 10 micrometers, along the dendrite, influencing nearby spines. The spreading is estimated to be about several tens of micrometers and potentially extends throughout a branch of dendrites. The Yasuda Lab had previously shown that stimulating just a few spines could lead to ERK activation in the nucleus, but they didn't know how this was achieved. This experiment showed that after these proteins are activated in a spine, the message spreads strongly over a long distance and potentially reaches the nucleus. "To find that PKA and ERK activation in spines is spreading for several tens of micrometers is certainly a surprising discovery for the field," said Tang.

The team has visualized an important step in the process, but there is still a long way to go to understanding the biochemical underpinnings of learning and memory.
-end-
About MPFI

The Max Planck Florida Institute for Neuroscience (Jupiter, Florida, USA) specializes in the development and application of novel technologies for probing the structure, function, and development of neural circuits. It is the first research institute of the Max Planck Society in the United States.

Max Planck Florida Institute for Neuroscience

Related Neurons Articles:

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.
Shaping the social networks of neurons
Identification of a protein complex that attracts or repels nerve cells during development.
With these neurons, extinguishing fear is its own reward
The same neurons responsible for encoding reward also form new memories to suppress fearful ones, according to new research by scientists at The Picower Institute for Learning and Memory at MIT.
How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
More Neurons News and Neurons Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 3: Shared Immunity
More than a million people have caught Covid-19, and tens of thousands have died. But thousands more have survived and recovered. A week or so ago (aka, what feels like ten years in corona time) producer Molly Webster learned that many of those survivors possess a kind of superpower: antibodies trained to fight the virus. Not only that, they might be able to pass this power on to the people who are sick with corona, and still in the fight. Today we have the story of an experimental treatment that's popping up all over the country: convalescent plasma transfusion, a century-old procedure that some say may become one of our best weapons against this devastating, new disease.   If you have recovered from Covid-19 and want to donate plasma, national and local donation registries are gearing up to collect blood.  To sign up with the American Red Cross, a national organization that works in local communities, head here.  To find out more about the The National COVID-19 Convalescent Plasma Project, which we spoke about in our episode, including information on clinical trials or plasma donation projects in your community, go here.  And if you are in the greater New York City area, and want to donate convalescent plasma, head over to the New York Blood Center to sign up. Or, register with specific NYC hospitals here.   If you are sick with Covid-19, and are interested in participating in a clinical trial, or are looking for a plasma donor match, check in with your local hospital, university, or blood center for more; you can also find more information on trials at The National COVID-19 Convalescent Plasma Project. And lastly, Tatiana Prowell's tweet that tipped us off is here. This episode was reported by Molly Webster and produced by Pat Walters. Special thanks to Drs. Evan Bloch and Tim Byun, as well as the Albert Einstein College of Medicine.  Support Radiolab today at Radiolab.org/donate.