Summary: Researchers identified a critical role for the gene KDM5B in learning and memory. Their study demonstrates that mice with reduced function of this gene exhibit significant deficits in memory and the ability to learn.
Experiments showed that KDM5B is essential for the strengthening of neuronal connections, crucial for memory formation. This discovery not only deepens understanding of cognitive functions but also opens new avenues for addressing intellectual disabilities and conditions like autism.
Key Facts:
- Gene Function in Memory: KDM5B plays a pivotal role in regulating the strength of neuronal connections, which is crucial for learning and memory.
- Impact on Intellectual Disability: While KDM5B has been linked to autism and intellectual disabilities, its direct impact on learning and memory provides new insights for potential therapeutic targets.
- Research Methodology: The study involved genetically modifying mice to reduce KDM5B function in adults, isolating the geneโs impact on learning from developmental effects, with significant findings regarding cognitive deterioration and epileptic seizures.
Source: University of Exeter
A gene previously linked to intellectual disability has been found to regulate learning and memory in mice.
The gene, called KDM5B has previously been linked to some intellectual disability disorders and autism. In the general population, some variants are also associated with reduced brain function, although not sufficient to cause an overt disability or behavioural symptoms.
Now, researchers at Kingโs College London, the University of Exeter and the University of California Irvine have found that reduced function of the gene in the brain results in loss of learning ability and memory and a reduction in the brainโs ability to strengthen connections between neurons, which is key in the formation of memories.
The teamโs new mouse study, published in theย Journal of Neuroscienceย describes how mice bred without a fully functionalย KDM5Bย gene have worse learning and memory abilities.
In order to rule out the possibility that the effect may have been caused by an impact on brain development, the researchers also reduced the amount of this gene in a separate group of adult mice, in the hippocampus, a brain region responsible for memory.
They found that reduced gene function resulted in epileptic seizures in some mice and a deterioration of their learning and memory. Laboratory experiments suggested that the strengthening of connections between neurons during memory formation was reduced.
Professor Albert Basson, whose research group began the work at Kingโs College London and has since moved to the University of Exeter, said: โMemory and the ability to learn are fundamental to our intellectual potential, yet we still have a lot to learn about the underpinning mechanisms.
“For more than a decade, theย KDM5Bย gene has been linked to autism and some forms of intellectual disability, but a mutation in this gene alone is not always sufficient to cause these conditions, so it hasnโt been studied in detail.
“Our work shows that KDM5B is important for learning and memory and provides new insight into the fundamental mechanisms of memory and learning, which is crucial on the pathway to finding new ways to improve these functions.โ
KDM5B can modify the structure of the genetic material in our cells which determines whether genes necessary for brain development or function are expressed at the correct amount at the right time.
Dr Leticia Peres-Sisquez who performed the research at Kingโs College London, said: โWe set out to investigate whetherย KDM5Bโsย ability to modify genetic material has a direct impact on learning and memory.
“Weโve discovered that the gene has a direct impact on learning and memory โ which is distinct from any effect during brain development. This gene will now be of much greater interest to researchers on the quest for new treatments for conditions including autism, and other intellectual disability disorders.โ
Funding: The research was funded by the Medical Research Council and the National Institutes of Aging, with support from Wellcome.
About this genetics, learning, and memory research news
Author: Louise Vennells
Source: University of Exeter
Contact: Louise Vennells – University of Exeter
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The intellectual disability risk gene Kdm5b regulates long term memory consolidation in the hippocampus” by Albert Basson et al. Journal of Neuroscience
Abstract
The intellectual disability risk gene Kdm5b regulates long term memory consolidation in the hippocampus
The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders, and heterozygous, protein-truncating variants inย KDM5Bย are associated with reduced cognitive function in the population.
The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity.
To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for aย Kdm5bฮARIDย allele that lacks demethylase activity.ย Kdm5bฮARID/ฮARIDย mice exhibited hyperactivity and long-term memory deficits in hippocampus-dependent learning tasks.
The expression of immediate early, activity-dependent genes was downregulated in these mice and hyperactivated upon a learning stimulus compared with wild-type (WT) mice. A number of other learning-associated genes were also significantly dysregulated in theย Kdm5bฮARID/ฮARIDย hippocampus.
Next, we knocked downย Kdm5bย specifically in the adult, WT mouse hippocampus with shRNA.ย Kdm5bย knockdown resulted in spontaneous seizures, hyperactivity, and hippocampus-dependent long-term memory and long-term potentiation deficits.
These findings identify KDM5B as a critical regulator of gene expression and synaptic plasticity in the adult hippocampus and suggest that at least some of the cognitive phenotypes associated withย KDM5Bย gene variants are caused by direct effects on memory consolidation mechanisms.
