Changing clocks and changing seasons: Scientists find role for neuronal plasticity

A team of scientists has linked changes in the structure of a handful of central brain neurons to understanding how animals adjust to changing seasons. Its findings enhance our understanding of the mechanisms vital to the regulation of our circadian system, or internal clock.

The work, which appears in the journal Cell, focuses on the regulation of "neuronal plasticity"--changes in neuronal structure--and its function in the brain.

"Neuronal plasticity underpins learning and memory, but it is very challenging to tie changes in specific neurons to alterations in animal behavior," explains Justin Blau, the paper's senior author and a professor in NYU's Department of Biology and at NYU Abu Dhabi. "In our research, we've discovered how plasticity of a very small number of neurons helps run the biological clock and aids transitions to different seasons."

The paper's other authors were Afroditi Petsakou, a recent PhD graduate from NYU's Department of Biology, and Themistoklis Sapsis, an assistant professor at MIT.

In their study, the researchers focused on the principal s-LNv clock neurons in the fruit fly Drosophila, which is commonly used for research on circadian rhythms--earlier studies of "clock genes" in fruit flies lead to the identification of similarly functioning genes in humans.

Specifically, their work centered on the ends/tips of the axons of these neurons, where they release their signals. Previous research had established that these termini change their structure with a 24-hour rhythm, but it was unclear what function these alterations served.

In the Cell study, the scientists quantified the daily changes in s-LNv axon termini and found that they grow and retract every 24 hours. They also identified the protein that drives these rhythms in neuronal plasticity: Rho1. Moreover, they found that plasticity of the s-LNvs is required both for maintaining circadian rhythms (the biological clock) and for allowing seasonal adaptation of these rhythms. Specifically, if s-LNvs are unable to retract then flies behave normally in winter but fail to predict the early dawn of long summer days. Conversely, if s-LNvs remain in a retracted state, then flies behave as if they are in summer on both short and long days.

They also found rhythms in the proteins at the ends of the s-LNv axons. At dawn, s-LNvs have high levels of proteins involved in sending signals and low levels of the proteins that allow them to receive signals. The opposite is true at dusk. This unusual type of neuronal plasticity suggests that the function of s-LNvs changes dramatically over the day: from mainly sending signals at dawn to mainly receiving signals at dusk.

The findings may also shed new light on a human affliction, spinocerebellar ataxia--a neurodegenerative disease that affects coordination and movement. Blau's group found that the daily changes in Rho1 activity are controlled by rhythms in transcription of a gene very similar to human Puratrophin-1.

"Since some forms of spinocerebellar ataxia are associated with mutations in human Puratrophin-1, our data support the idea that defective neuronal plasticity underlies loss of motor control and leads to neurodegeneration," notes Blau.

Study to investigate the economic benefits of musculoskeletal research to society, UK

A new study initiated this month by five leading research funders and institutions will estimate the health and economic benefits of UK investment in medical research into musculoskeletal conditions.

Supported by Arthritis Research UK, The Wellcome Trust, the Medical Research Council, the Department of Health and the Academy of Medical Sciences, this is the third in a series of health economic studies which have focused on the return on public and charitable investment in medical research.

Following previous studies on cardiovascular disease and cancer research, which demonstrated that medical research investment generates significant health and economic gains over the long term, the new study will focus on research into musculoskeletal conditions, including inflammatory forms of arthritis, conditions of musculoskeletal pain such as osteoarthritis, and osteoporosis.

The research team will be led by Professors Jonathon Grant (King's College London) and Martin Buxton (Health Economic Research Group, Brunel University). Supported by leading clinical experts from across the sector, they will identify the most important research-based interventions that have led to reduced morbidity and mortality from musculoskeletal disease and that have provided health gain over a 20-year period. Using their established methodology, the value of health gain from these interventions will be estimated, and set against the public and charity funding in the field. The wider economic benefits leveraged by research investment will also be considered.

For the first time, the study will also examine the international flow of knowledge into clinical guidelines and the extent of private funding leveraged by research.

Dr Liam O'Toole, chief executive officer at Arthritis Research UK said:
"Arthritis and musculoskeletal conditions affect ten million people in the UK. Everything we do is driven by knowledge to positively impact on what matters to people with arthritis. We are delighted to be working in partnership on this important study which will establish the benefits research has had on improving the health outcomes of people with arthritis. The findings will be of great interest."

Chief medical officer, Professor Dame Sally Davies said: "We want to make the NHS among the best in Europe at supporting people with long-term conditions such as arthritis and musculoskeletal conditions, and be confident that we are using research funds well to facilitate this. This latest study will quantify the value of the research funded by government and charities where the main outcome is an improved quality of life for patients."

Professor Sir John Tooke PMedSci, President of the Academy of Medical Sciences said: "In times of high competition for public funding, it is increasingly important to demonstrate the benefits of medical research to the economy as well as healthcare.

"The medical sciences community has demonstrated a long-standing commitment to evaluating the economic impact of its research.

"This new study represents the latest instalment of a larger programme aimed at quantifying the economic returns of different areas of medical research by the Academy and partners, which has so far considered cancer, cardiovascular disease and mental health."

Professor Jonathon Grant, director of the Policy Institute at King's College London said: "This study will complement previous work to assess the economic returns from biomedical and health research, and we are delighted to have this opportunity to validate and further refine our methodology.

"The impact of research on musculoskeletal disease is an important area to investigate because it is not dominated by changes in smoking behaviour, as in our studies on cardiovascular disease and cancer.

"Furthermore, changes to morbidity are much harder to measure than mortality and musculoskeletal disease has clear morbidity components involved such as treating back pain. We hope that this study will provide insight into the benefit of research to this range of diseases."