Researchers profile active genes in neurons based on connections

May 23, 2014
Researchers profile active genes in neurons based on connections
A new mouse TRAP: The team tested their profiling technique on midbrain mouse neurons (blue) that use the neurotransmitter dopamine to send signals to a brain region known as the nucleus accumbens. To do so, they tagged protein-assembling ribosomes (red) using a small antibody that bound a fluorescent protein (green).

(Medical Xpress)—When it comes to the brain, wiring isn't everything. Although neurobiologists often talk in electrical metaphors, the reality is that the brain is not nearly as simple as a series of wires and circuits. Unlike their copper counterparts, neurons can behave differently depending on the situation.

Researchers in Jeffrey Friedman's Laboratory of Molecular Genetics have devised a way to create snapshots of gene expression in neurons based on their connections. These snapshots contain exhaustive lists of the active genes within neurons that send information to a synapse, the junction between neurons.

Their new technique, called Retro-TRAP, merges two approaches to understanding the brain: mapping all of its connections and profiling gene expression within populations of neurons, Friedman says.  "We hope that Retro-TRAP will be broadly used and provide a more granular understanding of how complex neural circuits function and ultimately lead to better treatments for neurological and neuropsychiatric disorders."

"Refinements in neuroscience over time have allowed us to explore how the nervous system works in ever-greater detail, and the approach we have developed continues this trend," says Mats Ekstrand, a research associate in the laboratory. "By building on existing techniques, we are now able to take a closer look at the types of cells involved in a particular circuit and what they are doing."

In the long run, these sorts of insights might help explain why some diseases, such as Parkinson's Disease, afflict particular sets of neurons, or someday make it possible to precisely target treatments at a dysfunctional neural circuit, rather than bathing the entire brain in drug.

The researchers modified a technique known as translating ribosome affinity purification (TRAP), developed at Rockefeller by Nathaniel Heintz, Paul Greengard and others to identify gene expression using green fluorescent protein to tag protein-assembling machines called ribosomes.

In research published today in Cell, Ekstrand, graduate student Alexander Nectow and colleagues describe how they used Retro-TRAP to introduce green fluorescent protein to the neuron via a virus that travels backwards from a synapse into the body of a mouse neuron. The researchers used a small antibody to link the ribosome with the . Then, using these fluorescent tags, the researchers pulled out the ribosomes and sequenced the genetic messages passing through them. In this way, they produced a list of active genes.

To test their technique, the team focused on inputs to a well-studied part of the brain, the nucleus accumbens, which integrates information from throughout the brain, including regions involved in executive function, memory, depression, reward-related behavior, feeding and other functions, Nectow says.

"We wanted to target a selected number of inputs into the nucleus accumbens because we figured we might be able to get some molecular clues as to why it is important in regulating so many functions," Nectow says.

Using Retro-TRAP, they created molecular profiles of neurons extending from the hypothalamus and ventral midbrain that project to the nucleus accumbens. The results confirmed that Retro-TRAP works.

"The nucleus accumbens receives a lot of signals from the ventral midbrain via the neurotransmitter dopamine, and, as expected, the genes we sequenced included many associated with dopamine neurons," Nectow says.

Their data also contained some new discoveries. For instance, they found some neurons in the lateral hypothalamus express the p11 gene implicated in depression. After some further work, they found these neurons also tended to express a protein called orexin, a regulator of sleep and feeding—suggesting a molecular association between depression and some of its symptoms.

Retro-TRAP merges two approaches to understanding the brain: mapping all of the connections within it and profiling within populations of , Friedman says.  "We hope that Retro-TRAP will be broadly used and provide a more granular understanding of how complex neural circuits function and ultimately lead to better treatments for neurological and neuropsychiatric disorders."

Explore further: Studying behavior using light to control neurons

More information: "Molecular Profiling of Neurons Based on Connectivity." Mats I. Ekstrand, Alexander R. Nectow, Zachary A. Knight, Kaamashri N. Latcha, Lisa E. Pomeranz and Jeffrey M. Friedman Cell Volume 157, Issue 5, p1230–1242, 22 May 2014

Related Stories

Studying behavior using light to control neurons

May 15, 2014
A new paper published by OIST's Neurobiology Research Unit identifies some of the neurons responsible for behavioral decisions in rats.

Delving deep into the brain

May 1, 2014
Launched in 2013, the national BRAIN Initiative aims to revolutionize our understanding of cognition by mapping the activity of every neuron in the human brain, revealing how brain circuits interact to create memories, learn ...

Map of brain connections provides insight into olfactory system

May 16, 2014
The processing of sensory information in the brain involves a complex network of neural connections specific to each type of sensory input. Much is known about the neural wiring associated with most senses, but the deeper ...

Using rabies virus, researcher tracks inputs to dopamine neurons

June 6, 2012
A genetically-modified version of the rabies virus is helping scientists at Harvard to trace neural pathways in the brain, a research effort that could one day lead to treatments for Parkinson's disease and addiction.

For neurons in the brain, identity can be used to predict location

March 24, 2014
Throughout the world, there are many different types of people, and their identity can tell a lot about where they live. The type of job they work, the kind of car they drive, and the foods they eat can all be used to predict ...

Stimulating brain cells stops binge drinking, animal study finds

January 3, 2014
Researchers at the University at Buffalo have found a way to change alcohol drinking behavior in rodents, using the emerging technique of optogenetics, which uses light to stimulate neurons.

Recommended for you

The neural codes for body movements

July 21, 2017
A small patch of neurons in the brain can encode the movements of many body parts, according to researchers in the laboratory of Caltech's Richard Andersen, James G. Boswell Professor of Neuroscience, Tianqiao and Chrissy ...

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.