Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Breaking Down the Parkinson’s Pathway

Published: Wednesday, March 20, 2013
Last Updated: Wednesday, March 20, 2013
Bookmark and Share
New study is first to analyze how affected brain cells respond during different behavioral tasks.

The key hallmark of Parkinson’s disease is a slowdown of movement caused by a cutoff in the supply of dopamine to the brain region responsible for coordinating movement. While scientists have understood this general process for many years, the exact details of how this happens are still murky.

“We know the neurotransmitter, we know roughly the pathways in the brain that are being affected, but when you come right down to it and ask what exactly is the sequence of events that occurs in the brain, that gets a little tougher,” says Ann Graybiel, an MIT Institute Professor and member of MIT’s McGovern Institute for Brain Research.

A new study from Graybiel’s lab offers insight into some of the precise impairments caused by the loss of dopamine in brain cells affected by Parkinson’s disease. The findings, which appear in the March 12 online edition of the Journal of Neuroscience, could help researchers not only better understand the disease, but also develop more targeted treatments.

Lead author of the paper is Ledia Hernandez, a former MIT postdoc. Other authors are McGovern Institute research scientists Yasuo Kubota and Dan Hu, former MIT graduate student Mark Howe and graduate student Nuné Lemaire.

Cutting off dopamine

The neurons responsible for coordinating movement are located in a part of the brain called the striatum, which receives information from two major sources — the neocortex and a tiny region known as the substantia nigra. The cortex relays sensory information as well as plans for future action, while the substantia nigra sends dopamine that helps to coordinate all of the cortical input.

“This dopamine somehow modulates the circuit interactions in such a way that we don’t move too much, we don’t move too little, we don’t move too fast or too slow, and we don’t get overly repetitive in the movements that we make. We’re just right,” Graybiel says.

Parkinson’s disease develops when the neurons connecting the substantia nigra to the striatum die, cutting off a critical dopamine source; in a process that is not entirely understood, too little dopamine translates to difficulty initiating movement. Most Parkinson’s patients receive L-dopa, which can substitute for the lost dopamine. However, the effects usually wear off after five to 10 years, and complications appear.

To study exactly how dopamine loss affects the striatum, the researchers disabled dopamine-releasing cells on one side of the striatum, in rats. This mimics what usually happens in the early stages of Parkinson’s disease, when dopamine input is cut off on only one side of the brain.

As the rats learned to run a T-shaped maze, the researchers recorded electrical activity in many individual neurons. The rats were rewarded for correctly choosing to run left or right as they approached the T, depending on the cue that they heard.

The researchers focused on two types of neurons: projection neurons, which send messages from the striatum to the neocortex to initiate or halt movement, and fast-spiking interneurons, which enable local communication within the striatum. Among the projection neurons, the researchers identified two subtypes — those that were active just before the rats began running, and those that were active during the run.

In the dopamine-depleted striatum, the researchers found, to their surprise, that the projection neurons still developed relatively normal activity patterns. However, they became even more active during the time when they were usually active (before or during the run). These hyper-drive effects were related to whether the rats had learned the maze task or not.

The interneurons, however, never developed the firing patterns seen in normal interneurons during learning, even after the rats had learned to run the maze. The local circuits were disabled.

Restoring neuron function

When the researchers then treated the rats with L-dopa, the drug restored normal activity in the projection neurons, but did not bring back normal activity in the interneurons. A possible reason for that is that those cells become disconnected by the loss of dopamine, so even when L-dopa is given, they can no longer shape the local circuits to respond to it.

This is the first study to show that the effects of dopamine loss depend not only on the type of neuron, but also on the phase of task behavior and how well the task has been learned, according to the researchers. To glean even more detail, Graybiel’s lab is now working on measuring dopamine levels in different parts of the brain as the dopamine-depleted rats learn new behaviors.

The lab is also seeking ways to restore function to the striatal interneurons that don’t respond to L-dopa treatment. The findings underscore the need for therapies that target specific deficiencies, says Joshua Goldberg, a senior lecturer in medical neurobiology at the Hebrew University of Jerusalem.

The new study “refines our appreciation of the complexity of [Parkinson’s],” says Goldberg, who was not part of the research team. “Graybiel’s team drives home the message that dopamine depletion, and dopamine replacement therapy, do not affect brain dynamics or behavior in a uniform fashion. Instead, their effect is highly context-dependent and differentially affects various populations of neurons.”

The research was funded by the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the National Parkinson Foundation, the Stanley H. and Sheila G. Sydney Fund, a Parkinson’s Disease Foundation Fellowship and a Fulbright Fellowship.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Wednesday, April 27, 2016
Long-Term Drug Release
New tablet attaches to the lining of the GI tract, resists being pulled away.
Thursday, April 07, 2016
Pharmacy on Demand
New, portable system can be configured to produce different drugs.
Monday, April 04, 2016
A Programming Language for Living Cells
New language lets researchers design novel biological circuits.
Monday, April 04, 2016
Why Some Tumors Withstand Treatment
Mechanism uncovered that allows cancer cells to evade targeted therapies.
Thursday, March 17, 2016
Cancer Cells Remodel Environments Before Spreading
Researchers at MIT have found that the cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Wednesday, March 16, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
A New Way to Discover DNA Modifications
Researchers systematically find molecules that help regulate and protect DNA.
Wednesday, March 02, 2016
MIT Study: Carbon Tax Needed to Cut Fossil Fuel Consumption
Researchers at MIT have suggested that the technology-driven cost reductions in fossil fuels will lead the world to continue using all the oil, gas, and coal, unless governments pass new taxes on carbon emissions.
Thursday, February 25, 2016
Mapping Regulatory Elements
Systematically searching DNA for regulatory elements indicates limits of previous thinking
Wednesday, February 03, 2016
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
Living a “Mixotrophic” Lifestyle
Some tiny plankton may have big effect on ocean’s carbon storage.
Tuesday, February 02, 2016
Faster Drug Discovery?
Startup develops more cost-effective test for assessing how cells respond to chemicals.
Friday, January 29, 2016
No More Insulin Injections?
Encapsulated pancreatic cells offer possible new diabetes treatment.
Tuesday, January 26, 2016
Engineering Foe into Friend
Bose Grant awardee Jacquin Niles aims to repurpose the malaria parasite for drug delivery.
Monday, January 25, 2016
Scientific News
Computational Model Finds New Protein-Protein Interactions
Researchers at University of Pittsburgh have discovered 500 new protein-protein interactions (PPIs) associated with genes linked to schizophrenia.
Experimental Drug Cancels Effect from Key Intellectual Disability Gene
A University of Wisconsin—Madison researcher who studies the most common genetic intellectual disability has used an experimental drug to reverse — in mice — damage from the mutation that causes the syndrome.
MicroRNA Pathway Could Lead to New Avenues for Leukemia Treatment
Cancer researchers at the University of Cincinnati have found a particular signaling route in microRNA (miR-22) that could lead to targets for acute myeloid leukemia, the most common type of fast-growing cancer of the blood and bone marrow.
Bioreactors Ready for the Big Time
Bioreactors are passive filtration systems that can reduce nitrate losses from farm fields.
Analysis of Dog Genome will Provide Insight into Human Disease
An important model in studying human disease, the non-coding RNA of the canine genome is an essential starting point for evolutionary and biomedical studies – according to a new study led by The Genome Analysis Centre (TGAC).
‘Mini-Brains’ to Study Zika
Novel tool expected to speed research on brain and drug development.
Finding Factors That Protect Against Flu
A clinical trial examining the body’s response to seasonal flu suggests new approaches for evaluating the effectiveness of seasonal flu vaccines.
New Insights into Gene Regulation
Researchers have solved the three-dimensional structure of a gene repression complex that is known to play a role in cancer.
Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Common Class of Cancer Drugs May Not Lead to Cognitive Decline
UCLA study refutes 2015 research suggesting anthracyclines could cause memory loss, other impairments.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!