Two seemingly opposing forces in the brain really cooperate to improve memory formation

The brain allows organisms to learn and adapt to their environment. To do this, it literally modifies the connections, or synapses, between neurons, thus reinforcing significant patterns of neuronal activity in order to store information. The existence of this process – cerebral plasticity – has been known for some time.

But in reality, there are two different types of brain plasticity at work on synapses. One is "Hebbian plasticity"; Named after Donald Hebb, a pioneering neuroscientist, he effectively allows the recording of information in synapses. The other, more recently discovered, is homeostatic synaptic plasticity (HSP) and, like other homeostatic processes, such as maintaining a constant body temperature, its goal is to maintain stability. In this case, HSP ensures that the brain does not accumulate too much physical activity (as in epilepsy) nor becomes too silent (which accompanies the loss of synapses in the disease). # 39; Alzheimer's).

However, little is known about how these two types of plasticity actually interact in the brain. At present, a team of neuroscientists from the Center for the Unknown Champalimaud in Lisbon, Portugal, has begun to unravel the fundamental processes that occur in the synapse when the two mechanisms overlap. Their results were published in the journal iScience.

"In theory, both types of plasticity act as opposing forces," says Anna Hobbiss, first author of the new study led by Inbal Israely. "The Hebbian plasticity reacts to the activity of the synapses by urging them to become stronger, while HSP reacts by weakening them." We wanted to understand, at the cellular and molecular level, how the synapse treats these two forces when they are present at the same time."

In doing so, the authors showed that, contrary to expectations, the HSP facilitates Hebbian plasticity and thus influences the formation of memory and its learning. This means that these two types of plasticity "may not be such separate processes, but work together within the same synapses," says Israely.

The goal of the team was to determine the size changes of minute structures called dendritic spines, which are the "recipient" of the synapse. The size of these spines changes to reflect the strength of the synaptic connection.

The researchers studied mouse hippocampus cells, a crucial part of the brain for learning. In their experiments, they blocked activity in the cells by introducing a powerful neurotoxin called tetrodotoxin, thus simulating the loss of entry into a certain part of the brain. "Think of a person who suddenly becomes blind, resulting in a loss of contribution from the eyes to the brain," said Hobbiss.

Forty-eight hours later, they imitated a small recovery of activity in a single synapse by releasing some glutamate molecules onto single neural spines. This was made possible by a state-of-the-art high-resolution laser technology called two-photon microscopy, which allowed scientists to accurately visualize and target individual dendritic spines.

As the process evolved, the team closely monitored the evolution of the spine and noted various anatomical changes. First, the silence of any neuronal activity has made the thorns swell. "The thorns are like small microphones that, when there is silence, turn up the volume to try to catch any noise," says Hobbiss.

The scientists then activated individual spines with glutamate pulses and observed them for two hours. One of the things they thought they could do was that the size of the thorns would not grow bigger, since they had already increased their "volume" as far as it would go. But the opposite has happened: the thorns have grown even bigger, the smallest spines showing the strongest growth.

Finally, the authors also found growth of neighboring spines, even though the experiment was aimed at only one spine. "We found that after a lack of activity, other neighborhood spines grew, further strengthening the cell's sensitivity to restored neuronal transmission," Hobbiss explains. "Cells become more sensitive, more likely to code information, it's as if the" gain "had been increased."

"The fact that neighboring spines have developed with an active spine means that homeostatic plasticity alters one of the characteristics of information storage: plasticity is limited to the site of data entry" says Israely. "Thus, in this sense, the different mechanisms of plasticity that intervene in the neuron can cooperate to modify inputs and responses that respond to a stimulus, and I think this is an interesting discovery of our study."

Taken together, these results show that homeostatic plasticity can actually improve the plasticity of Hebbian, the type required to store information. "Our work adds a piece to the puzzle of how the brain performs one of its fundamental tasks: being able to code information while maintaining a stable level of activity," Hobbiss concludes.

The deregulation of homeostatic plasticity – the stabilizing one – is beginning to be implicated in human health, particularly neurodevelopmental disorders such as Fragile X syndrome and Rett syndrome as well as neurodegenerative ones like disease-related disease. # 39; Alzheimer's. "Maybe this balance is what allows us to learn new information while maintaining the stability of this knowledge throughout life," says Israely.

Explore further:
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More information:
Anna Felicity Hobbiss et al. Homeostatic Plasticity Scale of Dendritic Spine Volumes and Alters the Threshold and Specificity of Hebbian Plasticity, iScience (2018). DOI: 10.1016 / j.isci.2018.09.015