Down’s syndrome is the most common genetic cause of intellectual disability, triggered by an extra copy of chromosome 21.
Using genetically engineered mice that carry a copy of this additional human chromosome, researchers from Bristol University and University College London (UCL) discovered that increased expression of chromosome 21 genes disrupted the function of the key brain circuits involved in learning and memory.
These findings shed new light on the part of the brain’s vast neural network which contributes to these problems among people with Down’s.
Dr Matt Jones, lead author and MRC Senior Research Fellow at the School of Physiology and Pharmacology at Bristol University, said: “Abnormalities in the hippocampus have been shown before in other mouse models of Down’s syndrome, but the mouse model we used is a more accurate genetic mimic of the human syndrome.
“The wiring diagram of the brain is so massively interconnected, we need to consider how even subtle changes in one part of the brain can cause trouble for other nodes of the circuit.”
The brain processes of information through co-ordinated communication between networks of nerve cells, wired together in electrical circuits by junctions called synapses.
Using hi-tech microscopy, nerve cell recordings and maze testing, the researchers showed abnormal structure and function of synapses in the networks of the hippocampus in the mouse model of Down’s syndrome.
The hippocampus acts as a central hub for learning and memory, allowing people to integrate past experience with the current context.
The paper, published in the journal Nature Neuroscience, shows that dysfunction at the input synapses of the hippocampus propagates around hippocampal circuits in the mouse model of Down’s, resulting in unstable information processing by place cells and also impaired learning and memory.
Over the course of a lifetime, even subtle impairments of this type will profoundly influence intellectual abilities, the study found.
Dr Jonathan Witton, one of the authors at Bristol, added: “This study further highlights the vulnerability of the hippocampus to increased expression of chromosome 21 genes.
“Therapies which aim to normalise the function of these disrupted networks may be particularly beneficial as part of the future treatments of Down’s syndrome.
Pandora Summerfield, chief executive for Down’s Syndrome Scotland, said: “The University of Bristol and UCL team have made interesting advances in the understanding of the impact of Down’s on the brains of mice.
“We look forward to reading further research in the search to lessen impairment.”