MINI REVIEW article
Front. Synaptic Neurosci.
This article is part of the Research TopicGrey Matters in the Lab: Utilizing Human Brain Tissue for Basic Research, Disease Modeling and Drug DevelopmentView all 6 articles
Enhanced Information Processing in the Human Neocortex: Cellular Mechanisms and Translational Perspectives
Provisionally accepted
- 1Universita degli Studi di Modena e Reggio Emilia, Modena, Italy
- 2Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy
- 3Department of Biomedical Sciences, International School for Advanced Studies (SISSA), Trieste, Italy
- 4Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali, Florence, Italy
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Understanding the sophisticated cognitive abilities of the human brain requires understanding its cellular and synaptic components. While rodent studies provide foundational knowledge, recent research using freshly resected human neocortical and hippocampal tissue has revealed unanticipated distinctive cellular characteristics. These properties, identified through in vitro electrophysiology, anatomical reconstructions, and computational modelling, have profound implications for physiological processes and modulatory responses. Here we highlight and review a selection of key unique features of human neurons. Human layer 2/3 pyramidal cells exhibit exceptionally low specific membrane capacitance and distinctive ion channel kinetics. Moreover, human pyramidal-to-pyramidal connections display species-specific synaptic dynamics, recovering from short-term depression much faster than in rodents. We also highlight that human pyramidal neurons exhibit more elaborate dendritic trees, particularly perisomatic branching, and faster, more stable AP dynamics. Interestingly, these features allow higher-bandwidth information transfer, reflecting enhanced computational power. All these cell-level differences directly impact how circuits process information and respond to pharmacological interventions. Increasingly, drugs targeting ion channels or synaptic mechanisms are used but often display different efficacy or kinetics in human neurons compared to rodents, reflecting underlying biophysical disparities. Consequently, leveraging human brain tissue is key as it allows for the identification of human-specific drug targets and a more accurate understanding of disease mechanisms. This review highlights these crucial cellular distinctions and underscores the importance of exploiting resected human brain tissue for advancing central nervous system therapeutics.
Keywords: Action potential (AP) kinetics, AP dynamics, Dendritic trees, Human neurons, ion channel kinetics, layer 2/3 pyramidal cells, membrane capacitance, perisomatic branching
Received: 17 Dec 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Tore, Monni, Di Clemente and Giugliano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Alessio Di Clemente
Michele Giugliano
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