Researchers at IEM proved that neurons are able to sync their beats like wall clocks

News

A new study covered by the prestigious journal Cell Reports describes a major discovery by neuroscientists at the ELKH Institute of Experimental Medicine (IEM) led by Balázs Hangya MD, PhD. The researchers have observed that a group of neurons in the brain's medial septum, which show different frequencies of rhythmic activity when desynchronized can synchronize their rhythmic frequency with increasing activation, creating a synchronized brain rhythm.

To understand this phenomenon, we must go back almost 400 years. In 1665, the Dutch scientist and inventor Christian Huygens wrote a letter in which he reported a discovery that he termed called ‘odd sympathy’.  When he hung two of his recently invented pendulum clocks next to each other on a wooden beam, their oscillations became synchronized over time. Balázs Hangya's group has now succeeded in observing and confirming Huygens' synchronization of brain neurons.

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3D representation of the mouse septohippocampal system. The hippocampus is shown in yellow and the medial septum in red. (Designed with the Scalable Brain Atlas software by Dániel Schlingloff.)

It was already known that neurons in the brain often synchronize in ‘quasi-rhythmic’ activity, collectively generating ‘brain waves’ that are sometimes detectable even from outside the skull using electroencephalography. It has also been known that this synchronized rhythm helps neurons to exchange information efficiently to perform key functions such as learning, memory and attention, perception, and motion.  However, how these rhythms are generated, maintained, and abolished to fit ever-changing needs for seamless operation of the brain has not yet been clarified.

To investigate the brain's synchronization mechanisms, the research team recorded special neurons of a deep brain structure known as the medial septum. These neurons form a network of rhythm regulators, also known as pacemakers, which generate the 4-12 Hz theta rhythm in the hippocampus responsible for recording the traces of the events we experience, i.e. encoding episodic memory.  While it is well established that hippocampal theta oscillation is important for memory, the exact mechanism by which it is generated is not well understood.

With this in mind, Balázs Hangya's laboratory, in collaboration with other groups led by professors István Ulbert, Viktor Varga and Szabolcs Káli, investigated the medial septal pacemaker network in awake and anaesthetized mice and rats. The Huygens synchronization mechanism was present in all conditions studied and was even observed in a simplified computer model of the medial septal pacemaker network.

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Image of the hippocampal theta wave in anaesthetized rat (Electrical recording of Balázs Hangya depicted by Barnabás Kocsis.)

The authors hypothesize that the Huygens synchronization could represent a general synchronization mechanism across brain circuits in different species, including humans. The results are not only of significance to basic research. Synchronization mechanisms in the brain can break down as a result of disease, leading to memory problems and attention deficit. The same process can also contribute to the development of serious conditions such as schizophrenia. Researchers hope that a better understanding of how brain circuits synchronize may eventually lead to better therapies for these diseases.

Publication:

Barnabás Kocsis, Sergio Martínez-Bellver, Richárd Fiáth, Andor Domonkos, Katalin Sviatkó, Dániel Schlingloff, Péter Barthó, Tamás F. Freund, István Ulbert, Szabolcs Káli, Viktor Varga, Balázs Hangya (2022). Huygens synchronization of medial septal pacemaker neurons generates hippocampal theta oscillation. Cell Reports, Vol. 40. doi: 10.1016/j.celrep.2022.111149