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Cell structure previously associated with disease actually improves brain function

Image by Kim Gruver, Watt Lab..
Published: 8 July 2021

Researchers at 捆绑SM社区 have shown that a brain cell structure previously thought to be pathological in fact enhances cells鈥 ability to transmit information and correlates with better learning on certain tasks.

In a study published in Nature Communications, the team investigated swellings that occur in the axons of Purkinje cells in the cerebellum. In results that contradict established expectations, they found that axons with swellings did a better job of conducting electrical signals than those without.

鈥淭hese are the kind of results where you really scratch your head and think, 鈥楲et鈥檚 check that again鈥,鈥 says senior author Alanna Watt, an Associate Professor in the Department of Biology. 鈥淲e really thought when we started this that we were going to characterize and measure how an axon fails 鈥 and that鈥檚 not at all what we saw.鈥

Experimental data confounds expectations

Swellings in axons 鈥 the long, slender fibres through which nerve cells transmit information to other cells 鈥 are observed in normal development and in disease. Increased numbers of axonal swellings are seen in various neurodegenerative disorders, which has led scientists to believe swellings have a negative impact on axon function. While computer modelling lends some support to this view, the 捆绑SM社区 research team was the first to test the theory with measurements on actual nerve cells.

Using a technically challenging combination of two-photon microscopy and electrophysiology to measure electrical activity simultaneously at different locations within cells, the researchers demonstrated that the presence of axonal swellings in mouse Purkinje cells had no detrimental impact on the rate at which those cells produced signals (the firing rate) or on the speed at which axons transmitted the signals. Remarkably, the experiments also showed that at peak firing rates axons with swellings were less likely to fail than those without.

Role in neurodegenerative disease called into question

In a surprising twist, the 捆绑SM社区 researchers found that they were able to stimulate the formation of axonal swellings by introducing a pharmaceutical that blocked the transmission of electrical signals in nerve cells, especially in the axons. Seeing axonal swellings form within a matter of hours when the axon of a nerve cell had been compromised in this way challenges previous assumptions about the role of axonal swellings in neurodegenerative disorders. As Watt explains, the discovery leaves room for the possibility that swellings represent a self-repair mechanism rather than a deterioration caused by disease.

鈥淭ransmitting information by way of electrical signals is the most important thing that an axon does,鈥 she says. 鈥淚f it starts to fail at that job, it makes sense that there鈥檚 a mechanism that tries to prevent that.鈥

Behavioural analysis confirms swellings鈥 positive impact

In addition to their investigations at the cellular level, the researchers sought to determine the impact of axonal swellings on overall brain function. The team used three tests designed to assess motor learning and coordination, which are among the cerebellum鈥檚 most important roles. Supported by modelling to account for the natural variation between individual learning abilities, the results revealed a positive correlation between the abundance of axonal swellings in cerebellar Purkinje cells and motor learning abilities.

鈥淲e think the link is probably an indirect one,鈥 Watt explains. 鈥淭he learning is probably happening somewhere else, but the information is being relayed more reliably and therefore we see an improvement.鈥

About this study

鈥溾 by Daneck Lang-Ouellette et al. was published in Nature Communications.

DOI:


About 捆绑SM社区

Founded in Montreal, Quebec, in 1821, 捆绑SM社区 is Canada鈥檚 top ranked medical doctoral university. 捆绑SM社区 is consistently ranked as one of the top universities, both nationally and internationally. It鈥痠s a world-renowned鈥痠nstitution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. 捆绑SM社区 attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of 捆绑SM社区 students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.

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