MAY 17, 2017 04:15 PM PDT

New Connection Between Receptors Discovered in the Brain

WRITTEN BY: Carmen Leitch

Researchers at Tufts University School of Medicine have reported the discovery of a novel signaling pathway, and the findings may have implications for the treatment of schizophrenia. Two important molecules in the brain that have been associated with learning and memory are the N-methyl-D-aspartate receptor (NMDAR) and the alpha 7 nicotinic acetylcholine receptor (a7nAChR). This work, published in Neuron and described in the video, indicates that a special type of non-neuronal cell in the brain, astrocytes, link these receptors.

"The NMDAR is the most investigated receptor in neuroscience because it is essential to synaptic plasticity, which is instrumental in establishing and remodeling brain circuitry and is thought to be the cellular foundation of learning and memory," explained lead author of the report Thomas Papouin, Ph.D., Research Assistant Professor at Tufts School of Medicine. "The NMDAR is known to be activated by two chemicals: glutamate, which is supplied by neurons, and D-serine, which is supplied by astrocytes. While most research is focused on the role that neurons play in activating the NMDAR via glutamate, we focused on the role played by astrocytes through the release of D-serine."

The researchers utilized a mouse model and in vitro techniques and found that astrocytes modulate the levels of D-serine release in response to wakefulness, something the astrocytes monitor directly. For that, the cells use a7nAChR to sense the level of acetylcholine, which is released in the brains of both humans and rodents during wakefulness. If a mouse was more active, the investigators observed that higher levels of D-serine were released by the astrocytes, which promoted the activation of NMDARs. That was true whether the mice were active as part of a normal routine, or stimulated to be active during unusual times.

Research from Tufts University in the journal Neuron reports a new signaling pathway that directly connects major brain receptors associated with learning and memory. Astrocytes (fluorescing green cells above) are the key element that links the receptors. Neurons are red. / Credit: Thomas Papouin

"Astrocytes act like the dimmer control of a light," Papouin explained. "When the neuronal switch goes on, and glutamate is released, the setting of the astrocytic D-serine 'dimmer' determines the intensity of the NMDAR signal. During wakefulness, this dimmer is set on high - astrocytes provide a lot of D-serine - and this allows for a strong NMDAR signal. But during sleep or inactivity, it is set on low, allowing for a weaker signal."

This work could help provide a new way to approach the treatment of schizophrenia and may open new avenues for therapeutics.

"This is an exciting finding with direct relevance to development of new treatments for schizophrenia, which is characterized by low levels of D-serine and diminished NMDAR as well as a major loss of cholinergic function. Efforts to develop pharmaceuticals to address these deficits have so far been unsuccessful, but in our study we were able to enhance NMDAR function via D-serine by stimulating a7nAChRs with a drug that has been part of recent stage 3 clinical trials for schizophrenia," said corresponding author Philip G. Haydon, Ph.D., the Annetta and Gustav Grisard professor and chair of the Department of Neuroscience at Tufts School of Medicine. "This suggests that cholinergic drugs now under development for schizophrenia work through this newly discovered astrocytic pathway."

 

Related: Special Lecturer - NMDAR dysfunction in schizophrenia: Implications for pathophysiology and basic neuroscience


Sources: AAAS/Eurekalert! via Tufts University, Neuron

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
NOV 16, 2018
Microbiology
NOV 16, 2018
Testing the Impact of a Low-gluten Diet on Healthy People
Gluten-free diets have exploded in popularity in recent years, even for people who don't have documented food allergies....
NOV 26, 2018
Neuroscience
NOV 26, 2018
Most Rewarding Experiences Take The Top Spot In Memory
brain filters out neutral, inconsequential events, retaining only the memories that are useful to the future decisions....
DEC 01, 2018
Videos
DEC 01, 2018
Identifying Disease-causing Gene Mutations
Genetic diseases can be traced back to an error in a gene. This video explores how the process works....
DEC 03, 2018
Genetics & Genomics
DEC 03, 2018
Reducing the Potential for Negative Side Effects in CRISPR
CRISPR-Cas9 is an amazing gene-editing tool, but there are some drawbacks. This work aims to fix that....
DEC 08, 2018
Cell & Molecular Biology
DEC 08, 2018
Regenerating Beta Cells to Cure Diabetes
Beta cells of the pancreas produce a critical hormone that controls blood sugar - insulin. But beta cells can die off....
DEC 10, 2018
Neuroscience
DEC 10, 2018
Brain's Dopamine: The Good, The Bad and The Ugly
Dopamine in the brain is an important neurotransmitter that is often attributed to pleasure chemical. But that's not all it does; research has identified the role of dopamine in fear, emotion...
Loading Comments...