Mechanisms of fast signaling in human neurons and their link to cognition

Our brain processes information through electrical signaling by its neurons. Because of difficult access to living human neurons, their function in supporting cognition remains largely unexplored. If we want to understand the biological basis of human cognition, we need to focus on human neurons and mechanisms underlying their computation. A critical requirement of fast neuronal computation is the ability of neurons to generate fast and stable output - action potentials. Indeed, I recently showed that fast action potential signaling directly links to cognitive ability in the same individuals. In addition, we recently demonstrated that human neocortex contains neuron types not found in other mammals and these types are selectively vulnerable in brain disorders with cognitive decline. According to my preliminary data, exactly these neuron types have surprisingly fast signaling. How do these human-specific neurons achieve fast cellular computation supporting human cognition? Here, I aim to study which cellular and molecular mechanisms drive fast and stable signaling in human neuron types. I will link these data to human cognition by investigating how and which genes of intelligence associate with fast signaling in specific neuron types. These questions can only now be addressed with our recent transcriptomic, morpho-electric Patch-RNA-sequencing technique applied to human neurons. Combined with molecular interventions and computational modeling, I will provide a novel mechanistic understanding of fast cellular computation mechanisms in human cortex. This will help explain how selective loss of neuron types in human brain disorders gives rise to cognitive decline. My strong publication record in applying novel, original approach to study human neuron function in relation to cognition puts me in a unique position to address this. Finally, my work is the first to take a cellular perspective on human cognition and establishes a unique research line: Human Cellular Cognitive Neurosciences.