"What makes the brain of Homo sapiens unique? A closer look at key parts of the organ shows that our brain isn't simply scaled up from the animal. It communicates more precisely and can store more information.
What's true for E. coli must also be true for the elephant," the pioneer of molecular biology, Jacques Monod, once said. This means that bacteria and elephants are biologically similar in many ways. When it comes to the brain, however, things get complicated. The human brain is difficult for science to study. Neuroscientists therefore generally rely on imaging techniques such as magnetic resonance imaging or animal studies.
Much of what we know about the human brain is based on experiments with rats or mice. This is especially true since comparative brain researchers are discovering more and more characteristics that were already present in the closest common ancestors of mice, humans, and elephants. Biologists also refer to these as "evolutionarily conserved" characteristics. But can data from mice and rats be so easily extrapolated to humans? And if so, what makes us unique?
Neuroscientist Peter Jonas from the Institute for Science and Technology Austria (ISTA) in Klosterneuburg near Vienna addressed precisely this question. He wanted to know whether the uniqueness of the human brain can be explained precisely by the high number of nerve cells – a human has 16 billion (1,000,000,000 is 1 billion) nerve cells in the brain, compared to only 71 million in mice – or whether human nerve cells and synapses have specific properties that make them species-specific and unique.
His findings were recently published in the journal "Cell." Born in Darmstadt, Peter Jonas improved electrophysiology techniques early in his career. After completing his doctorate, the physician worked in the laboratory of Bert Sakmann, who received the Nobel Prize in Medicine for developing the so-called patch-clamp technique [1]. A technique that allows scientists to read the currents of individual cells or even their components, such as synapses. They can use it to observe how ions flow into and out of the cell. Whether, for example, neighboring cell B also receives a stimulus when cell A is excited.
Jonas also learned about the hippocampus early on, the region responsible for transferring memories from short-term to long-term memory. In other words, how memories and locations are stored and retrieved in the hippocampus.
The hippocampus is considered one of the most studied brain regions today. No other region has been studied as much as the hippocampus. After all, it is also relevant in aging processes such as dementia.
What Peter Jonas didn't have at the beginning of his studies, however, was human tissue or the opportunity to test his hypotheses. When he was establishing the new Austrian Cluster of Excellence for Neuroscience, he discovered an opportunity: As part of epilepsy treatment at the Medical University of Vienna, some patients have to have the hippocampus removed on one side of the brain. Peter Jonas then collaborated with the Department of Neurosurgery at the Medical University of Vienna. When an epilepsy patient was due for surgery, Peter Jonas received notification the day before. For him and his research group, this meant dropping everything and working into the night. "We try to gather as much data as possible and examine the tissue for ten or twelve hours until we can't do anything else," says Jonas. The result was a broad physiological and anatomical characterization of the hippocampus. Jonas was surprised by the comparative studies: "When you work with rats and mice, you sometimes get the feeling that everything is already known about the hippocampus. But as soon as I started working on human samples, I realized how little we actually knew."
The neurons of the human hippocampus are less interconnected than those of a mouse, but they communicate with each other more precisely. Furthermore, human neurons can store more information than those of a mouse.
So, if you tried to extrapolate from a mouse hippocampus to a human hippocampus, you would underestimate some properties and overestimate others.
Dietmar Schmitz, director of the Charité Neuroscience Research Center, also works on the hippocampus and was impressed when he first saw Jonas's results. "In fact, there is very little work on the human hippocampus, which is why this study is particularly important, remarkable, and impressive," Schmitz said. On the one hand, the technique used is very difficult, and on the other hand, the hippocampal subregion analyzed — the so-called area CA3—very complex to study because the cells easily die during dissection. Schmitz, however, points to a similar study by Chris McBain from 2023. In the study, the authors concluded that evolutionarily conserved characteristics predominate between humans and mice, but in the eyes of South African brain researcher Paul Manger, one cannot simply extrapolate from a mouse brain. "Every species is unique in its own way. This is determined by how the species interacts with its natural environment." Manger works at the University of Witwatersrand in Johannesburg and is known for his comparative brain research, which ranges from mice to dolphins to African elephants. A dolphin has different ecological specializations than an elephant. Such differences are also reflected in the anatomy of the brain. Nevertheless, there are striking similarities: "Within an animal order, there is a relationship between neuron number and brain weight," says Manger. For him, Jonas's study is also of great value for animal research.
Jonas is already planning further studies with human brain tissue. He wants to find out even more about the human brain. He is motivated by the challenge of conducting experiments that seem impossible to others. "With some projects, you initially think it's impossible, but you manage it anyway. Sometimes, however, you have to wait until the right opportunity for an experiment arises." Regarding animal research, Jonas says, "Mice or rats will continue to be the gold standard in brain research. Our studies were only possible because our measurement techniques in animal models were well established and clear working hypotheses existed thanks to previous research." In the future, he hopes that neurological research will be able to help people with psychiatric illnesses. "But we're still at the very beginning here," Jonas points out.” [2]
1. The patch-clamp technique is an electrophysiological method that allows researchers to record and measure the flow of ions across biological membranes through ion channels, either at the whole-cell or single-channel level. The technique is used to study the electrical properties of excitable cells and ion channels, providing insights into cellular function and regulation at a molecular level. A glass micropipette, containing an electrolyte solution, is used to form a tight, high-resistance seal (gigaohm seal) with the cell membrane.
2. Von Maus zu Mensch? Frankfurter Allgemeine Zeitung; Frankfurt. 05 Mar 2025: N2. Von Felix Schmidtner
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