ISTA biologists team up with neurosurgeons to unravel the human brain’s specificities

Many of us have relished those stolen moments with a grandparent by the fireplace, our hearts racing to the intrigues of their stories from good old times, recounted with vivid imagery and a pinch of fantasy. Our human brain has a remarkable capacity for storing and recollecting memories over a lifetime. A physical space, a smell, or a familiar situation can alone bring back a memory, and our brain uses these associations to complete the pattern. Although the human brain is optimized for this purpose, we are only starting to understand how it integrates information about our surroundings. This pattern-completion process is a remarkable computational property of our brain called associative memory.
The bulk of our neuroscience knowledge about the brain stems from well-studied animal models, like rodents, which are indispensable for science. But is the human brain simply a scaled-up version of the mouse brain, or does it have distinct features that make it human? Now, researchers at the Institute of Science and Technology Austria (ISTA) and neurosurgeons at the Medical University of Vienna shed light on how the human brain forms and retrieves associative memories. Magdalena Walz Professor for Life Sciences at ISTA Peter Jonas and ISTA postdoc Jake Watson, who initiated the collaboration with Professor Karl Rössler from the Department of Neurosurgery of the Medical University of Vienna, examined samples from epilepsy patients who underwent neurosurgery to gain insights directly from intact, living human tissue.

Distinct human features of memory formation
The brain’s center for learning and associative memory is the hippocampus. Within it, a region called CA3 is responsible for storing and processing information and completing patterns. Because healthy human material is scarce, most studies have so far focused on animal models. Jonas and Watson overcame this problem by teaming up with Rössler, a neurosurgeon specializing in treatment-resistant forms of epilepsy. "While patients undergoing neurosurgery have a wide variety of clinical presentations, Prof. Rössler identified a subpopulation of epilepsy patients who presented an intact hippocampus," says Jonas. The scientists could not possibly miss this opportunity. "In this form of epilepsy, a unilateral resection of the hippocampus is necessary to ensure the patients have a chance to recover and lead an epilepsy-free life," explains Jonas. Thus, the team could obtain intact hippocampal tissue from 17 epilepsy patients with informed consent.

The researchers combined cutting-edge experimental techniques-multicellular patch-clamp recording to measure dynamic functional properties of neurons and super-resolution microscopy-with modeling and made eye-opening findings. Far from being a scaled-up version of the well-studied mouse hippocampus, the neural connectivity in the human CA3 region was sparser, and its synapses-the connections that allow signals to be passed between the neurons-appeared more reliable and precise. Thus, the team uncovered distinct properties of the human brain’s wiring.
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Publication:

Human tissue samples were obtained with informed patient consent from 17 individuals with temporal lobe epilepsy. This work was approved by the Ethics Committee of the Medical University Vienna (MUW) (EK Nr: 2271/2021). Further information can be found in the paper’s experimental model and study participant details section.