The search for a mechanism that could explain how the protein complex NCOR1/2 regulates memory has revealed an unexpected connection between the lateral hypothalamus and the hippocampus, the feeding and the memory centers of the brain, respectively. The findings, which were published in the journal Nature Neuroscience, have implications for studies on brain function, including those related to autism spectrum disorders, intellectual disabilities and neurodegenerative disease.
"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.
In this project, the researchers worked with mice carrying mutations of NCOR1/2. "These mice clearly present with memory deficits," said co-first author. "The signaling involving GABA, a key inhibitory neurotransmitter in the brain, was dysfunctional in hypothalamus neurons when NCOR1/2 was disrupted."
To explore the cellular mechanism underlying the condition, the researchers conducted a number of electrophysiological experiments to investigate how the lack of NCOR1/2 resulted in memory deficits in 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,"the author said. "It surprised us because the hypothalamus is not traditionally considered to be a major regulator of learning and memory."
The researchers validated the newly discovered circuits in different ways. "We applied both optogenetics and chemogenetics techniques," said co-first author. "The protein complex NCOR1/2 is key to the hypothalamus-hippocampus circuit; when we knock it out the circuit becomes dysfunctional."
In addition, the researchers have connected their findings in mouse models with human conditions. "We describe here new genetic variants of NCOR1/2 in patients with intellectual disability or neurodevelopmental defects," said co-corresponding author.
"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," co-corresponding author explains. "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."
These findings have implications for the relationships among endocrine factors, obesity and metabolic disorders and cognitive dysfunctions such as Alzheimer's disease. It is known, for instance, that people with endocrine disruption or metabolic disorders are more susceptible to Alzheimer's disease.
"Mechanisms underlying these associations are not completely clear," the senior author 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."
https://www.nature.com/articles/s41593-018-0311-1
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Gene to regulate sleep!
Read more
Why do we still have mitochondrial DNA?
Read more
New mathematical model to explain human genome mutation variability
Read more
Mutation in bile acid receptor identified!
Read more
A gene associated with a set of poorly understood rare diseases ide…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar