Circadian activity and plasticity of the brain

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Our brains surprise us with its unique properties. One of them is the circadian plasticity. Let's have a closer look at it from a twenty-four hour perspective.

When we learn or memorize certain information, some changes in the shape of neural cells (neurons and glial cells) and the connections between them (synapses) take place in our brains. These changes are referred to, respectively, as neural plasticity and synaptic plasticity. Such changes occur not only under the influence of external stimuli, such as learning, but also spontaneously during the day, and they persevere in spite of the lack of daily changes of day and night, in so-called fixed experimental conditions, e.g., in permanent darkness, which means that they are generated by the circadian clock.

What does this mean? The circadian clock, i.e., a group of special neurons, generates circadian changes in various processes in the body, also including the number of synapses and the structure of neurons. This means that when the body reaches the moment of peak activity during the day, some changes also take place in the brain, enabling more efficient reception, transmission, and processing of an increased amount of information.

We already know this, but we still do not know how the information from the biological clock is transmitted to neural cells in the brain or how it influences the architecture and function of those cells.

Plasticity – property consisting of the ability to maintain deformations (changes) that occurred at the moment of the activity of a specific factor.

The brain has a clock

The team, supervised by Professor Elżbieta Pyza from the Department of Cell Biology and Imaging of the Jagiellonian University, is attempting to solve this puzzle. Research on commonly known fruit flies (Drosophila) and mice has proven that changes occurring in neural cells of the brain throughout the day depend on the activity of the so-called "clock genes," and that the signal from the "internal clock" is transmitted to target cells with the use of special chemical substances – neuropeptides. They control, for example, the flow of ions through cellular membranes, which leads to cyclical changes in the volume of the cells, i.e., the cyclical neuronal plasticity.

Recent studies have shown that the regulation of circadian rhythms at the level of individual brain cells is very complex. Not only the primary clock (in the fruit fly it consists of approximately 150 neurons, which are characterized by an expression of the clock genes and spontaneous circadian neural activity) works in the brain, but also circadian oscillators in some glial cells of the brain and in peripheral organs, such as, for example, photoreceptors in the compound eye of the fruit fly. Within the visual system, the circadian rhythm of changes in the volume and shape of neurons is controlled not only by the primary clock, but also by endogenous, molecular oscillators located in glial cells and photoreceptors.

Imaging of the fruit fly brain using confocal microscope


How does the clock signal reach individual neurons in the brain?

Clock neurons transmit information by means of releasing specific neuropeptides, which, in turn, control the activity of the ion pump – the sodium and potassium pump, i.e., specific proteins in the cellular membrane which actively transport ions of sodium and potassium through the membrane. The sodium and potassium pump is present in each cell, regulating numerous cellular processes and the activity of the cell. After each change in the concentration of sodium ions flowing into the cell, the sodium pump expels such ions from the cell, introducing potassium ions so the cell returns to its resting potential.

If the clock information from the primary clock and other oscillators reaches the cell, the activity of the pump in neurons and glial cells changes within 24 hours and is the highest during the peak activity period of the body and the lowest during sleep. Moreover, the circadian clock also influences the level of other proteins from which synapses are constructed.

Apart from that, it has been proven that with age, circadian plasticity changes in the brain become less noticeable and that they are additionally reduced by the influence of toxic substances present in food, such as lead, cadmium, zinc, and aluminium, whose ions are released, e.g., from aluminium pots during cooking.

"The studies will provide us with knowledge about crucial genes and proteins encoded by such genes necessary to maintain circadian neuronal and synaptic plasticity and about certain factors (diet, motoric activity, and toxic substances) influencing this process," Professor Pyza explained.  

In the future, knowledge about "clock genes" and factors influencing circadian changes in neuronal plasticity will contribute to the development of a therapy improving the functioning of the brain and delaying neuron degenerative processes, which are characteristic of conditions such as Alzheimer's disease.

Research team: Professor Elżbieta Pyza; Jolanta Górska-Andrzejak, PhD; Grzegorz Tylko, PhD; Milena Damulewicz, PhD; Wojciech Krzeptowski, PhD; Olga Woźnicka, PhD; Danuta Semik, PhD; Alicja Gorlich, MSc; Elżbieta Guzik, MSc; Ewelina Kijak; Joanna Strzęp; Lucyna Walkowicz