Nav: Home

Scientists track unexpected mechanisms of memory

October 03, 2016

DURHAM, N.C. -- Do you remember Simone Biles's epic gymnastics floor routine that earned her a fifth Olympic medal? Our brains hold on to memories like these via physical changes in synapses, the tiny connections between neurons.

A new study by researchers at Duke University and the Max Planck Florida Institute for Neuroscience reveals unexpected molecular mechanisms by which these changes take place. Published in advance online Sept. 28 in the journal Nature, the findings could also shed light on how some diseases develop, including certain forms of epilepsy.

"We're beginning to unlock some of the mysteries underlying both the acquisition of a memory in the normal brain, as well as how a normal brain is transformed into an epileptic brain," said the study's co-senior investigator James McNamara, M.D., a professor in the departments of neurobiology and neurology at Duke University.

As we acquire a new memory, the connections, or synapses, between certain sets of neurons strengthen. In particular, the receiving end of a pair of these neurons -- consisting of a little nub called a spine -- gets a little larger.

Researchers have long suspected that a brain receptor called TrkB was involved with the growth of spines when we learn, but the new study confirms that the receptor is indeed crucial and delves further into how it works.

The key technologies that enabled this finding included a molecular sensor that the group developed to track activity of TrkB, and microscopes that allowed them to visualize a single spine in the area of living mouse brain tissue, all in real time.

The group also was able to add a tiny amount of signaling chemical, glutamate, at the single spine in order to mimic what happens during learning. This caused the spines to grow.

"The mouse brain has approximately 70 million neurons, and most of them are dotted with thousands of spines," McNamara said. "So, to be able to model and study the events occurring in a single spine in a single neuron is remarkable."

Without the TrkB receptor, spine growth did not occur in response to the signaling chemical, the group found.

The team suspected that yet another player, brain-derived neurotrophic growth factor (BDNF), was involved because it is the molecular key to TrkB's lock. The scientists created a molecular sensor for BDNF and showed that mimicking the signal associated with learning caused the release of BDNF from the receiving end of the synapse. This was surprising because conventional wisdom holds that BDNF is only released from the sending neuron, not the receiving neuron.

The fact that the receiving neuron both discharges BDNF into the gap between neurons and also senses it is "extremely unique, biologically," said co-senior investigator Ryohei Yasuda, scientific director of the Max Planck Florida Institute for Neuroscience. "One possibility is that BDNF is regulating several surrounding cells at once. We're interested in following up to understand the exact process."

Although the experiments were conducted in mice, the interaction between TrkB and BDNF is likely to be important for learning and memory in people, McNamara said.

What's more, the same mechanisms are likely at play in one of the most common forms of epilepsy, called temporal lobe epilepsy (TLE), which targets brain regions responsible for learning and memory.

Some cases of TLE are thought to be caused by a single, prolonged episode of seizures early in life. During the episode, glutamate, the same neurochemical involved in memory is released, but at much higher levels and for much longer times. McNamara's previous work shows that the TrkB receptor is critical for development of TLE, and last fall his group showed that inhibiting TrkB signaling briefly following the first seizure episode prevents the development of TLE in mice.

McNamara's group is carrying out additional experiments to understand what happens after TrkB is activated in order for single spines to get bigger. In addition, other mechanisms are likely contributing to TrkB activation in both memory and epileptic episodes, and McNamara's group is exploring other potential mechanisms.
-end-
The research was supported by the National Institutes of Health (F31NS078847, R01NS068410, DP1NS096787, R01NS05621, R01MH080047, R01DA08259, R01HL098351, P01HL096571, and RO1NS030687) the Wakeman Fellowship, and Human Frontier Science Program.

CITATION: "Autocrine BDNF-TrkB Signalling Within a Single Dendritic Spine," Stephen C. Harward, Nathan G. Hedrick, Charles E. Hall, Paula Parra-Bueno, Teresa A. Milner, Enhui Pan, Tal Laviv, Barbara L. Hempstead, Ryohei Yasuda, and James O. McNamara. Nature, advance online Sept. 28, 2016. DOI: 10.1038/nature19766

Duke University

Related Neurons Articles:

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.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
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.
Neurons that fire together, don't always wire together
As the adage goes 'neurons that fire together, wire together,' but a new paper published today in Neuron demonstrates that, in addition to response similarity, projection target also constrains local connectivity.
Scientists accidentally reprogram mature mouse GABA neurons into dopaminergic-like neurons
Attempting to make dopamine-producing neurons out of glial cells in mouse brains, a group of researchers instead converted mature inhibitory neurons into dopaminergic cells.
More Neurons News and Neurons Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.