Featured Research

from universities, journals, and other organizations

Active genes in neurons profiled based on connections

Date:
May 23, 2014
Source:
Rockefeller University
Summary:
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.

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).
Credit: Image courtesy of Rockefeller University

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 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 fluorescent protein. 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 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."


Story Source:

The above story is based on materials provided by Rockefeller University. Note: Materials may be edited for content and length.


Journal Reference:

  1. MatsI. Ekstrand, AlexanderR. Nectow, ZacharyA. Knight, KaamashriN. Latcha, LisaE. Pomeranz, JeffreyM. Friedman. Molecular Profiling of Neurons Based on Connectivity. Cell, 2014; 157 (5): 1230 DOI: 10.1016/j.cell.2014.03.059

Cite This Page:

Rockefeller University. "Active genes in neurons profiled based on connections." ScienceDaily. ScienceDaily, 23 May 2014. <www.sciencedaily.com/releases/2014/05/140523145135.htm>.
Rockefeller University. (2014, May 23). Active genes in neurons profiled based on connections. ScienceDaily. Retrieved August 20, 2014 from www.sciencedaily.com/releases/2014/05/140523145135.htm
Rockefeller University. "Active genes in neurons profiled based on connections." ScienceDaily. www.sciencedaily.com/releases/2014/05/140523145135.htm (accessed August 20, 2014).

Share This




More Health & Medicine News

Wednesday, August 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
Powered by NewsLook.com
American Ebola Patient Apparently Improving, Outbreak Is Not

American Ebola Patient Apparently Improving, Outbreak Is Not

Newsy (Aug. 19, 2014) Nancy Writebol, an American missionary who contracted Ebola, is apparently getting better, according to her husband. The outbreak, however, is not. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins