Molecular memories mark males from females
Medical Research Council scientists have found that males and females have different ways of remembering things.
In a test, male mice learned to avoid a dangerous situation better than females. In other tasks, there was no difference in learning performance, but there were different molecules in the brain being used to form the memories.
The work will help scientists to understand memory-related diseases, which affect the sexes to different extents.
“There’s clear evidence now from our studies that at the molecular level there is a sex difference,” said Professor Peter Giese, who led the study. “Our science would suggest that males and females simply use different memory processes.”
Professor Giese describes his research in an MRC podcast. This work at the Institute of Psychiatry, King’s College London, was supported by the MRC.
In the task, the team placed mice in a chamber and attempted to train them to avoid a potentially dangerous situation. They subjected the animals to a mild electric shock to their feet while playing them an audio signal.
Compared with females, a higher proportion of males learned to physically freeze when they were returned to the chamber and then exposed to the sound signal, associating this environment and the tone with danger. This ability to learn was absent in genetically-engineered male mice – but not female mice – which lacked a certain brain protein involved in the regulation of memory genes.
“We think that we have a window into understanding the molecular basis of sex differences in memory formation,” said Professor Giese.
The protein, called CaMKK, may function abnormally in some brain diseases and cognitive disorders. This finding could help to understand why some brain diseases affect different proportions of women and men, such as Alzheimer’s disease, schizophrenia and learning disabilities.
The protein CaMKK has a role in the process believed to underlie what happens in the brain when a memory is laid down and stored. This model of learning, established in 1973 by MRC-funded researcher Dr Tim Bliss at the National Institute for Medical Research (NIMR), is called long-term potentiation.
Dr Bliss said: “If long-term potentiation is the basis of memory, then one might predict that in animal models of Alzheimer’s disease there should be an impairment of long-term potentiation. In many cases there is.”
MRC scientists have found that mice with Down’s syndrome – a symptom of which in humans is impaired learning ability – have deficits in long-term potentiation and memory. In 2005, a team at NIMR created a model of a Down’s syndrome by engineering a mouse which contains an extra chromosome, the cause of the syndrome in humans, press release.
Dr Bliss said: “In most mouse models of Alzheimer’s disease, there is an impairment in long-term potentiation. This is also true in models of neurodegenerative and other sorts of diseases in which memory is affected, including Down’s syndrome as we recently showed.”
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Background
Professor Giese published his findings in the following papers:
Mizuno et al. (2007). Calcium/calmodulin kinase kinases β has a male-specific role in memory formation. Neuroscience, 145, 393.
Antunes-Martins et al. (2007). Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation. Learn. Mem. 14, 693.
Mizuno et al. (2006). Ca2+/calmodulin kinase kinase α is dispensable for brain development but is required for distinct memories in male, though not in female, mice. Mol. Cell. Biol. 26, 9094.
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MRC units and institutes where memory and learning research takes place
National Institute for Medical Research, http://www.nimr.mrc.ac.uk/
Anatomical Neuropharmacology Unit, http://mrcanu.pharm.ox.ac.uk/
MRC Cognition and Brain Sciences Unit, http://www.mrc-cbu.cam.ac.uk/
MRC Centre for Neurodegeneration Research, http://cnr.iop.kcl.ac.uk/
