X-linked mental retardation protein is found to mediate synaptic plasticity in hippocampus
Scientists at Cold Spring Harbor Laboratory (CSHL) have solved part of a puzzle concerning the relationship between changes in the strength of synapses the tiny gaps across which nerve cells in the brain communicate and dysfunctions in neural circuits that have been linked with drug addiction, mental retardation and other cognitive disorders.
A team led by CSHL Professor Linda Van Aelst has pieced together essential steps in a signaling cascade within excitatory nerve cells that explains a key phenomenon called longterm depression, or LTD. The "depression" in question has nothing to do with the human illness with that name. Rather, it refers to a tamping-down of the strength of individual synapses what scientists call synaptic plasticity.
The mechanism behind LTD is called endocytosis. It involves a retraction of receptors where neurotransmitters can "dock." Van Aelst and colleagues have demonstrated how LTD works following activation of a class of receptors called group I metabotrobic glutamate receptors, or mGluRs.
It was known that longterm depression mediated by mGluRs depended in part on the rapid synthesis of specific proteins. Yet the identity of these proteins had largely remained a mystery. The CSHL scientists have now shown that locally rapid production of a protein called oligophrenin 1 (OPHN1) follows activation of group I mGluRs. OPHN1 in turn was shown to mediate LTD in hippocampal nerve cells, by interacting with yet another protein called EndophilinA2/3.
The result of this cascade of intracellular signals was dramatic: persistent removal of AMPA-type receptors at the excitatory synapse, and the onset of LTD. When rapid production of OPHN1 was blocked, mGluR-dependent LTD did not occur. These findings appear online today ahead of print in the journal Neuron.
Van Aelst explained the significance of the finding. "OPHN1 has two important functions that we know about. One is early in development, after synapses have appeared in the emerging nervous system. In this phase, OPHN1 in concert with other factors stabilizes receptors at synapses, and thus is essential in maintaining the structure of these essential features of neural circuitry.
"Our new findings show another vital role for OPHN1, later in development and into maturity. We assume that in response to behavioral stimuli we aren't yet sure what kind mGluRs are activated, setting off the series of steps that we identified: rapid upregulation of OPHN1, which binds to EndophilinA2/3, which in turn mediates the long-term removal of AMPA receptors."
OPHN1 is known to be associated with X-linked mental retardation and with other cognitive and behavioral deficits. The team hypothesizes that OPHN1-related changes in plasticity such as those described in their new work may be causally related to such pathology. They are investigating this possibility in their current work.
More information: "Rapid Synthesis of the X-linked Mental Retardation Protein OPHN1 Mediates mGluR-Dependent LTD through Interaction with the Endocytic Machinery" appears online ahead of print October 19 in Neuron.
Provided by Cold Spring Harbor Laboratory
- Protein linked to mental retardation controls synapse maturation, plasticity Jun 01, 2009 | not rated yet | 0
- Neuroscientists show insulin receptor signaling regulates structure of brain circuits Jun 19, 2008 | not rated yet | 0
- Scientists reveal molecular sculptor of memories Sep 26, 2011 | not rated yet | 0
- The APCs of nerve cell function Jun 16, 2008 | not rated yet | 0
- MIT reports key pathway in synaptic plasticity May 21, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
14 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
Neuroscience 38 minutes ago | not rated yet | 0 |
(Medical Xpress)—The human brain is able to identify individuals' voices by comparing them against an internal 'average voice' prototype, according to neuroscientists.
Neuroscience 4 hours ago | 1 / 5 (1) | 0 |
A new study determined that children and adolescents with seizures involving the temporal lobe are likely to have clinically significant behavioral problems and psychiatric illness, especially depression. Findings published ...
Neuroscience 4 hours ago | not rated yet | 0
As the human body fine-tunes its neurological wiring, nerve cells often must fix a faulty connection by amputating an axon—the "business end" of the neuron that sends electrical impulses to tissues or other ...
Neuroscience 6 hours ago | 5 / 5 (2) | 0 |
A study by researchers at Henry Ford Hospital found "substantial evidence" that a regenerative process involving damaged nerve fibers in the spinal cord could hold the key to better functional recovery by most stroke victims.
Neuroscience 6 hours ago | not rated yet | 0 |
Two out of five medical students have an unconscious bias against obese people, according to a new study by researchers at Wake Forest Baptist Medical Center. The study is published online ahead of print in the Journal of ...
12 minutes ago | not rated yet | 0
International efforts to combat a new pneumonia-like virus that has now killed 22 people are being slowed by unclear rules and competition for the potentially profitable rights to disease samples, the head ...
13 minutes ago | not rated yet | 0
Breast cancer characterized as "triple negative" carries a poor prognosis, with limited treatment options. In some cases, chemotherapy doesn't kill the cancer cells the way it's supposed to. New research from Western University ...
49 minutes ago | 5 / 5 (1) | 0
Mayo Clinic researchers have used next generation genomic analysis to determine that some of the more aggressive prostate cancer tumors have similar genetic origins, which may help in predicting cancer progression. The findings ...
53 minutes ago | not rated yet | 0
(HealthDay)—A shortage of a critical tuberculosis drug has hampered the efforts of health departments across the United States to contain the spread of the highly infectious lung disease, federal officials ...
53 minutes ago | not rated yet | 0
(AP)—Merck & Co. says it is ending development of an experimental Parkinson's disease drug because the drug wasn't working.
29 minutes ago | not rated yet | 0