New findings of cortical activity during delta wave sleep sheds further light into memory formation

Scientists at the Center for Interdisciplinary Research in Biology have shown that delta waves emitted while we sleep are not generalized periods of silence during which the cortex rests, as has been described for decades in the scientific literature. Instead, they isolate assemblies of neurons that play an essential role in long-term memory formation. These results were published in journal Science.

While we sleep, the hippocampus reactivates itself spontaneously by generating activity similar to that while we are awake. It sends information to the cortex, which reacts in turn. This exchange is often followed by a period of silence called a ‘delta wave’ then by a rhythmic activity called a ‘sleep spindle’. This is when the cortical circuits reorganize to form stable memories.

However, the role of delta waves in the formation of new memories is still a puzzle: why does a period of silence interrupt the sequence of information exchanges between the hippocampus and the cortex, and the functional reorganization of the cortex?

The authors here looked more closely at what happens during delta waves themselves. They discovered, surprisingly, that the cortex is not entirely silent but that a few neurons remain active and form assemblies, i.e. small, coactive sets that code information. This unexpected observation suggests that the small number of neurons that activate when all the others stay quiet can carry out important calculations while protected from possible disturbances.

And the discoveries from this work go even further! Spontaneous reactivations of the hippocampus determine which cortical neurons remain active during the delta waves and reveal transmission of information between the two cerebral structures. In addition, the assemblies activated during the delta waves are formed of neurons that have participated in learning a spatial memory task during the day. Together these elements suggest that these processes are involved in memory consolidation.

To demonstrate it, in rats the scientists caused artificial delta waves to isolate either neurons associated with reactivations in the hippocampus or random neurons. Result: when the right neurons were isolated, the rats managed to stabilize their memories and succeed at the spatial test the next day.

Effects of flu on brain

Group of researchers from Germany and USA studied effects of influenza virus on brain cells. The study published in the Journal of Neuroscience finds that female mice infected with two different strains of the flu shows changes in structure and function of the hippocampus. These changes persist for one month after infection.

The long-term effect of influenza A virus infection on glial cell density and activation status within the hippocampal subregions. The neurotropic H7N7 IAV infection induced an increased microglia density in all hippocampal subregions at 30 days post-infection. Credit: Hosseini et al., JNeurosci

Influenza could present with neurological symptoms in some cases. So far research has not studied the long-term effect of the virus in the brain.

Researchers investigated three different influenza strains (H1N1, H3N2, H7N7). Two of these strains, H3N2 and H7N7, caused memory impairments that were associated with structural changes such as dendritic spine loss to neurons in the hippocampus. These changes persist up to 30 days following infection and fully recovered in 120 days.

Researchers feel that in the acute phase of influenza infection, this neuroinflammation in hippocampus alters the neuronal morphology and can cause cognitive deficits. The results also provide evidence that neuroinflammation induced by influenza virus infection can lead to longer-lasting alterations in neuronal connectivity with associated impairments in spatial memory formation.

Citation: Hosseini, Shirin, Esther Wilk, Kristin Michaelsen-Preusse, Ingo Gerhauser, Wolfgang Baumgärtner, Robert Geffers, Klaus Schughart, and Martin Korte. “Long-term neuroinflammation induced by influenza A virus infection and the impact on hippocampal neuron morphology and function.” The Journal of Neuroscience, 2018, 1740-17. doi:10.1523/jneurosci.1740-17.2018.

Research funding: Ministry of Science and Culture of Lower Saxony, Helmholtz-Association.

Adapted from press release by the Society for Neuroscience.

Research shows musicians have faster reaction to sensory stimuli

According to a new study by Université de Montréal’s School of Speech-Language Pathology and Audiology, part of UdeM’s medical faculty learning to play musical instrument help elderly to react faster and to stay alerted. The study is published in journal Brain and Cognition.  The study shows that musicians have faster reaction times to sensory stimuli than non-musicians have.

Credit: Pexels/pixabay

According to lead researcher Simon Landry, this study has implications for preventing some effects of aging. “The more we know about the impact of music on really basic sensory processes, the more we can apply musical training to individuals who might have slower reaction times,” Landry said.

In his study, co-authored with his thesis advisor, audiology associate professor François Champoux, Landry compared the reaction times of 16 musicians and 19 non-musicians. Research subjects sat in a quiet, well-lit room with one hand on a computer mouse and the index finger of the other on a vibrotactile device, a small box that vibrated intermittently. They were told to click on the mouse when they heard a sound (a burst of white noise) from the speakers in front of them, or when the box vibrated, or when both happened.

Each of the three stimulations – audio, tactile and audio-tactile – was done 180 times. The subjects wore earplugs to mask any buzzing “audio clue” when the box vibrated. “We found significantly faster reaction times with musicians for auditory, tactile and audio-tactile stimulations,” Landry writes in his study.

“These results suggest for the first time that long-term musical training reduces simple non-musical auditory, tactile and multisensory reaction times.” The musicians were recruited from UdeM’s music faculty, started playing between ages 3 and 10, and had at least seven years of training. There were eight pianists, 3 violinists, two percussionists, one double bassist, one harpist and one viola player. All but one (a violinist) also mastered a second instrument or more. The non-musicians were students at the School of Speech-Language Pathology. As with the musicians, roughly half were undergraduates and half graduates.

Landry, whose research interest is in how sound and touch interact, said his study adds to previous ones that looked at how musicians’ brains process sensory illusions. “The idea is to better understand how playing a musical instrument affects the senses in a way that is not related to music,” he said of his study.

Citation: Landry, Simon P., and François Champoux. “Musicians react faster and are better multisensory integrators.” Brain and Cognition 111 (2017): 156-162.
DOI: 10.1016/j.bandc.2016.12.001
Research funding: Canadian Institutes of Health Research, Fonds de recherche Québec – Santé, and Natural Sciences and Engineering Research Council of Canada.
Adapted from press release by the Université de Montréal.

Biomarker Autotaxin, related to diabetes predicts Alzheimer’s disease outcome

An enzyme found in the fluid around the brain and spine is giving researchers a snapshot of what happens inside the minds of Alzheimer’s patients and how that relates to cognitive decline.

Iowa State University researchers say higher levels of the enzyme, autotaxin, significantly predict memory impairment and Type 2 diabetes.  Autotaxin often studied in cancer research, is an even stronger indicator of Type 2 diabetes. A single point increase reflects a 300 percent greater likelihood of having the disease or pre-diabetes. The results are published in the Journal of Alzheimer’s Disease. Willette and Kelsey McLimans, a graduate research assistant, say the discovery is important because of autotaxin’s proximity to the brain.

“We’ve been looking for metabolic biomarkers which are closer to the brain. We’re also looking for markers that reliably scale up with the disease and have consistently higher levels across the Alzheimer’s spectrum,” said Auriel Willette, an assistant professor of food science and human nutrition at Iowa State. “This is as directly inside of the brain as we can get without taking a tissue biopsy.”

Willette’s previous research found a strong association between insulin resistance and memory decline and detrimental brain outcomes, increasing the risk for Alzheimer’s disease. Insulin resistance is a good indicator, but Willette says it has limitations because what happens in the body does not consistently translate to what happens in the brain. That is why the correlation with this new enzyme found in the cerebrospinal fluid is so important.

“It has a higher predictive rate for having Alzheimer’s disease,” McLimans said. “We also found correlations with worse memory function, brain volume loss and the brain using less blood sugar, which has also been shown with insulin resistance, but autotaxin has a higher predictive value.”

The fact that autotaxin is a strong predictor of Type 2 diabetes and memory decline emphasizes the importance of good physical health. Researchers say people with higher levels of autotaxin are more likely to be obese, which often causes an increase in insulin resistance. Willette says autotaxin levels can determine the amount of energy the brain is using in areas affected by Alzheimer’s disease. People with higher autotaxin levels had fewer and smaller brain cells in the frontal and temporal lobes, areas of the brain associated with memory and executive function. As a result, they had lower scores for memory and tests related to reasoning and multitasking.

Researchers analyzed data from 287 adults collected through the Alzheimer’s Disease Neuroimaging Initiative, a public-private partnership working to determine whether MRI and PET scans as well as biological markers can measure the progression of cognitive impairment and Alzheimer’s disease. The data came from adults ranging in age from 56 to 89 years old. Study participants completed various tests to measure cognitive function. This included repeating a list of words over various time increments.

Citation: McLimans, Kelsey E. and Auriel A. Willette. “Autotaxin is Related to Metabolic Dysfunction and Predicts Alzheimer’s Disease Outcomes”. Journal of Alzheimer’s Disease Volume 56, Number 1.
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Research funding: Iowa State Presidential Initiative for Interdisciplinary Research and National Institutes of Health.
Adapted from press release by Iowa State University.

Exercise improves memory in Diabetic rats

University of Tsukuba led researchers shows that moderate exercise may improve hippocampal memory dysfunction caused by type 2 diabetes and that enhanced transport of lactate to neurons may be the underlying mechanism.

Type 2 diabetes is characterized by impaired glucose metabolism and can cause central nervous system-related complications, such as memory dysfunction. The hippocampus is an essential brain component for normal memory formation. However, the effect of impaired glycometabolism on hippocampal-mediated memory in type 2 diabetes patients is not known.

In a new study, researchers centered at the University of Tsukuba investigated whether hippocampal glucose metabolism and memory function are altered in a rat model of type 2 diabetes. Based on the idea that exercise normalizes glycometabolism and improves memory function, the research team also investigated the effects of exercise on hippocampal glycometabolism and memory formation.

The hippocampal function was evaluated by placing the rat in a circular pool and testing its ability to remember the location of a platform that would allow it to escape from the water. “This is a well-established method for measuring spatial learning and memory,” study first author Takeru Shima says.

Type 2 diabetic rats needed more time to escape the water and find the platform. However, after 4 weeks of moderate exercise, they were able to find the platform much faster. “This indicated that exercise significantly improved spatial memory impairments in type 2 diabetic rats,” Shima explains.

Glycogen levels are altered in tissues of diabetes patients, leading to a variety of complications. However, glycogen levels have not yet been investigated in the hippocampus. “We showed for the first time that glycogen levels are significantly higher in the hippocampus of diabetic rats,” corresponding author Hideaki Soya says.

Interestingly, a single bout of exercise reduced hippocampal glycogen levels and this correlated with an increase in lactate levels. Lactate is an energy substrate and neuromodulator in the hippocampus and is known to enhance memory formation. Lactate is transferred to neurons through monocarboxylate transporters (MCTs). “MCT2 expression was significantly lower in the hippocampus of type 2 diabetic rats,” Soya says, “dysregulated MCT2-mediated neuronal uptake of lactate is a possible etiology of memory dysfunction in type 2 diabetes, and that elevated hippocampal glycogen may be an adaptive change to compensate for the decreased lactate utilization”.

4 weeks of moderate exercise further enhanced glycogen levels and normalized MCT2 expression in the hippocampus of type 2 diabetic rats.” These findings suggest that disrupted MCT2-mediated uptake of lactate by neurons contributes to memory dysfunction in type 2 diabetic rats.

The findings indicate that moderate exercise could be used to treat memory impairment in patients with type 2 diabetes by promoting the transfer of glycogen-derived lactate to hippocampal neurons. Further research is needed to see if this correlates in human beings.

Citation: Shima, Takeru, Takashi Matsui, Subrina Jesmin, Masahiro Okamoto, Mariko Soya, Koshiro Inoue, Yu-Fan Liu, Ignacio Torres-Aleman, Bruce S. McEwen & Hideaki Soya. “Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes.” Diabetologia 2016 pp: 1-10.
DOI: 10.1007/s00125-016-4164-4
Research funding: Ministry of Education, Culture, Sports, Science and Technology – Japan, Japan Society for the Promotion of Science.
Adapted from press release by University of Tsukuba.