JAN 21, 2019 06:19 PM PST

Linking the Brain's Memory and Hunger Control Center

WRITTEN BY: Carmen Leitch

In the brain, a region called the hypothalamus is known to play a role in the control of hunger, while the hippocampus functions in learning and memory. Now researchers have found a link between those two areas. Reporting in Nature Neuroscience, the team learned more about how neurons change when molecules called NCOR1 and NCOR2 (NCOR1/2) are lost, and the resulting impact on memory in a mouse model. The work may help researchers understand neurological problems including autism spectrum disorder, intellectual disability, and neurodegenerative disease.

Image credit: Pixabay

"It was not known how NCOR1/2 regulates memory or other cognitive functions, but there is evidence that NCOR1/2 plays a fundamental role in the activity of many hormones," said the corresponding author of the report Dr. Zheng Sun, an assistant professor of medicine and of molecular and cellular biology at Baylor College of Medicine.

The researchers used a mouse model for this work that carried mutations in the NCOR1/2 genes. "These mice clearly present with memory deficits," noted the study's co-first author Dr. Wenjun Zhou, a postdoctoral researcher in the Sun lab. "The signaling involving GABA, a key inhibitory neurotransmitter in the brain, was dysfunctional in hypothalamus neurons when NCOR1/2 was disrupted."

In this work, the scientists used electrophysiology to understand the memory defects in the NCOR1/2-deficient mice.

"What struck us the most was that the process by which NCOR1/2 regulates memory involves a new circuit that links two brain regions: the lateral hypothalamus, known as a feeding center of the brain, and the hippocampus, a place that stores memory," said study collaborator Dr. Yong Xu, an associate professor of pediatrics, molecular and cellular biology at Baylor. "It surprised us because the hypothalamus is not traditionally considered to be a major regulator of learning and memory."

The investigators used several techniques to validate their findings, including optogenetics, in which gene expression is modulated with a laser. "We applied both optogenetics and chemogenetics techniques," said the co-first author of the study Dr. Yanlin He, a postdoctoral associate in the Xu lab. "The protein complex NCOR1/2 is key to the hypothalamus-hippocampus circuit; when we knock it out the circuit becomes dysfunctional."

The researchers followed up on their findings in humans and were able to show that people with problems in their NCOR genes also have neurological issues.

"We describe here new genetic variants of NCOR1/2 in patients with intellectual disability or neurodevelopmental defects," explained the co-corresponding report author Dr. Pengfei Liu, an assistant professor of molecular and human genetics at Baylor and laboratory director of clinical research at Baylor Genetics.

"The gene NCOR1 is located on human chromosome 17, very close to the region that has been previously implicated in the Potocki-Lupski and Smith-Magenis syndromes," added Liu. "We have always suspected that mutations of this gene could cause intellectual disabilities or other deleterious neurological consequences. The mouse models in the current study provide the first evidence that this is indeed the case."

An increasing body of evidence is linking metabolic disorders to dementia and Alzheimer’s disease. This work may help begin to show how the problems are connected in the brain.

"Mechanisms underlying these associations are not completely clear," Sun said. "We think that the NCOR1/2-regulated neural circuit between the feeding and the memory centers of the brain we have discovered is worth exploring further in this context."

The video above from Mayo Clinic asks whether Alzheimer's disease is a third type of diabetes. 

Sources: AAAS/Eurekalert! via Baylor College of Medicine, JAMA NeurologyNature Neuroscience

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
OCT 22, 2019
Genetics & Genomics
OCT 22, 2019
Using CRISPR to Edit the DNA Carried by Human Sperm
Efforts to edit the human genome are rolling forward, despite a call for a moratorium on heritable edits....
OCT 22, 2019
OCT 22, 2019
Researchers Reconstruct the HIV Genome From a Sample Taken in 1966
Now there is biological evidence that the virus infected people in Africa before it was identified in the US....
OCT 22, 2019
OCT 22, 2019
Neuroscientists create a stunning digital map of 1,000 neurons
Two years ago, Dr. Jayaram Chandrashekar and his colleagues at the Howard Hughes Medical Institute's Janelia Research Campus sought out to map the mouse brain as intricately as possible. Now,...
OCT 22, 2019
Cell & Molecular Biology
OCT 22, 2019
Using CRISPR to Track and Image Genome Editing in Real Time
A team of scientists use fluorescently labeled proteins and CRISPR technology to image DNA transcription and chromosomal rearrangements....
OCT 22, 2019
Cell & Molecular Biology
OCT 22, 2019
A Molecular Connection Between Depression and Chronic Pain is IDed
The stress of chronic pain has been known to be associated with depression for many years, and scientists have been studying the basis of that connection....
OCT 22, 2019
Cell & Molecular Biology
OCT 22, 2019
Light Therapy Developed for Treating Carbon Monoxide Poisoning
According to the Centers for Disease Control and Prevention, everyone is at risk from carbon monoxide (CO) poisoning....
Loading Comments...