Silence to think: special interneuron networks in the human brain

Overview: Human cortical networks have evolved a new neural network that relies on abundant connections between inhibitory interneurons.

Source: Max Planck Institute

The analysis of the human brain is a central goal of neuroscience. However, for methodological reasons, research has largely focused on model organisms, especially the mouse.

Now neuroscientists have gained new insights into human neural circuitry using tissue obtained from neurosurgical interventions. Three-dimensional electron microscope data revealed a new extensive network of interneurons in humans compared to mice.

The discovery of this prominent network component in the human cortex stimulates further detailed analysis of its function in health and disease.

At first glance, mouse and human brains are surprisingly similar: the nerve cells that make up our brains have very similar shapes and properties, the molecular mechanisms of electrical excitation are highly conserved, and many biophysical phenomena found in other species, also seem to apply to human brains.

“So, is it mainly the fact that our brains are 1000 times bigger, contain 1000 times more nerve cells that allow us to play chess and write children’s books, which arguably mice can’t do?” asks Moritz Helmstaedter, director of the Max Planck Institute for Brain Research (Frankfurt), which led the new study, published June 23 in the journal Science

By analyzing the neuronal networks in mice, monkeys and humans and mapping their entire structure in biopsies of brain tissue called connectomes, Helmstaedter and his team found that human cortical networks have evolved a new type of neuronal network that is essentially absent in mice. This neuronal network depends on abundant connections between inhibitory interneurons.

Using biopsies from neurosurgical interventions performed by neurosurgeon Hanno-Sebastian Meyer and his team at TU Munich, the researchers applied three-dimensional electron microscopy to map about one million synapses in human brain samples.

Their data revealed in humans an unexpected bias of interneurons (enriched in humans) connecting with each other, while innervation (synaptic connections) with the main neurons remained largely similar.

“This suggests to us an almost 10-fold expansion of an interneuron-to-interneuron network,” said Sahil Loomba, one of the lead authors of the studies.

“Interneurons make up about one-fourth to one-third of cortical nerve cells that behave in a very peculiar way: they are very active, however, not to activate other neurons, but to silence them. Just like the kindergarten caretakers, or the guards in the museum, their very labour-intensive and very energy-consuming activity is to keep others calm and quiet,” explains Helmstaedter.

Human neuronal networks, mapped from different parts of the cerebral cortex. Mouse connectomic comparison revealed vastly extensive interneuron-to-interneuron networks in humans. Credit: Loomba, Helmstaedter, MPI for brain research; Loomba et al., Science

“Now imagine a room full of museum guards, all silencing each other. This is what the human brain has evolved!”

But what could this mean? Theoretical work has suggested that such networks of mufflers can extend the time in which recent events in the neuronal network can be preserved: expanding working memory.

“In fact, it’s highly likely that longer working memory will help you perform more complex tasks and increase your reasoning ability,” Helmstaedter says.

The new discovery suggests a first clear network innovation in humans that deserves intensive further study.

He adds: “It can also be a site of pathological change and should be studied in the context of neuropsychiatric disorders. Last but not least, none of the main AI methods today use such interneuron-to-interneuron networks.”

About this neuroscience research news

Author: Irina Epstein
Source: Max Planck Institute
Contact: Irina Epstein – Max Planck Institute
Image: The image is credited to Loomba, Helmstaedter, MPI for Brain Research; Loomba et al., Science

Also see

Here's a diagram from the study:

Original research: Closed access.
“Connectomic Comparison of Mouse and Human Cortex” by Moritz Helmstaedter et al. Science


Abstract

Connectomic Comparison of Mouse and Human Cortex

The human cerebral cortex is home to 1,000 times more neurons than a mouse’s cerebral cortex, but the possible differences in synaptic circuitry between these species are still poorly understood.

We used three-dimensional electron microscopy of mouse, macaque and human cortical samples to study their cell type composition and synaptic circuit architecture.

The 2.5-fold increase in interneurons in humans compared to mice was offset by a change in axonal connection probabilities and therefore did not yield a commensurate increase in inhibitory-versus-excitatory synaptic input balance on human pyramidal cells.

Rather, increased inhibition created an extensive interneuron-to-interneuron network, driven by an expansion of interneuron-targeting interneuron types and an increase in their synaptic selectivity for interneuron innervation.

These are the major neuronal network changes in the human cortex.

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