17 Dec 2019

Neurons that sync together link together

Neurons that fire together wire together is a famous phrase to describe how the brain adjusts connections between its neurons. And while this certainly is at the heart of how the brain learns, it might be only part of the story. A new study, co-authored by ESI scientist Wolf Singer, provides evidence that neural plasticity as we know it, is gated by a higher order mechanism that depends on synchronized activity of local networks.

We continue to learn throughout life. That doesn’t necessarily mean that we study for another university degree every month, but there are small changes in our environment all the time that we have to adjust to. Like when your colleague moves the coffee mugs to another shelf, or when you go on holiday to Switzerland and have to deal with a foreign currency. The basis of lifelong learning is a process called neuronal plasticity, which is the brain’s ability to change the wiring of its neurons. Connections between neurons are strengthened or weakened depending on how often they are active at the same time. “Neurons that fire together, wire together” is how scientists like to describe this simple but effective rule.

Now, neurons can be quite busy being excited about all sorts of input. Accordingly, rewiring is a very flexible process. It can happen very rapidly, but be reversed just as quickly. However, to introduce long-lasting changes, just firing together is not enough. The stimulus causing the excitation also has to be relevant; it has to fulfil certain criteria of validity. According to Wolf Singer, Senior Director at the Ernst Strüngmann Institute, this makes a lot of sense: “This way the brain makes sure not to introduce non-sensical modifications that would render it dysfunctional.” But how does the brain do that? How does it make sure all conditions in favour of a long lasting change are met?

Creating long lasting connections between neurons

Wolf Singer and his colleagues Ralf Galuske and Matthias Munk suspected local network dynamics in the so-called gamma-band between 20 and 48Hz as a promising candidate mechanism, which pushes short lived “wiring together” into long lasting neural connections. In order to test this idea, the scientists needed to set up a stable experimental condition, in which the only thing that would change was the presence or absence of precise synchrony of neuronal discharges. Such precise synchronisation of firing occurs when neuron populations engage in gamma oscillations. In previous experiments they found a way to do exactly that: In cats the occurrence of gamma oscillations in the primary visual cortex (V1) can be evoked by pairing visual stimulation with electrical stimulation of a particular area in the midbrain, the midbrain reticular formation. This stimulus configuration often but not always induces gamma oscillations in V1. If synchronized network activity is indeed a significant factor in defining a relevant stimulus, long term changes should happen only when oscillations are present.

Stimulus preference of orientation selective neurons in V1 is modulated by gamma oscillations (image credit: Ralf Galuske)

Stimulus preference of orientation selective neurons in V1 is modulated by gamma oscillations (image credit: Ralf Galuske)

This was exactly what the scientists found to be true in their experiment. Parallel to the electrical stimulation of the midbrain, they visually stimulated orientation selective neurons in V1 with gratings of different orientations. By measuring the orientation selectivity of these neurons both with optical and electrical recording techniques, they found that with time, the orientation preferred by the neurones started to drift towards that of the presented stimulus. If oscillations were weak or absent, the responses of the stimulated neurons became weaker but did not change their orientation preferences.

These results indicate that synchronized population responses at gamma-frequencies could be an important mechanism to regulate neuronal plasticity. “The idea is not new” summarizes Wolf Singer. “But we never had direct experimental evidence to back it up.” With the latest results at hand, scientists might have to expand the notion of “firing together” to include gating by precise temporal synchronisation.

Original publication: Galuske RAW, Munk HJM, Singer W (2019). Relation between gamma oscillations and neuronal plasticity in visual cortex. Proc Natl Acad Sci USA 116(46), 23317-23325. https://doi.org/10.1073/pnas.1901277116