Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Axonal and dendritic recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Experimentally-based detailed biophysical models have shown that the key factor responsible for the accelerated EPSP propagation in human cortical dendrites is the large conductance load imposed at the soma by the large basal dendritic tree. Additionally, larger dendritic diameters and differences in cable and ion channel properties in humans contribute to enhanced signal propagation. Our integrative experimental and modeling study provides new insights into the scaling rules that help maintain information processing speed albeit the large and sparse neurons in the human cortex.

Neurovascular coupling, linking neuronal activity to cerebral blood flow, is essential for brain function and underpins functional brain imaging. Whereas mechanisms involved in vasodilation are well-documented, those controlling vasoconstriction remain overlooked. This study unravels the mechanisms by which pyramidal cells elicit arteriole vasoconstriction. Using patch-clamp recording, vascular and Ca²⁺ imaging in mouse cortical slices, we show that strong optogenetic activation of layer II/III pyramidal cells induces vasoconstriction, correlating with firing frequency and somatic Ca²⁺ increase. Ex vivo and in vivo pharmacological investigations indicate that this vasoconstriction predominantly recruits prostaglandin E2 through the cyclooxygenase-2 pathway, and activation of EP1 and EP3 receptors. We also present evidence that specific interneurons releasing neuropeptide Y, and astrocytes, through 20-hydroxyeicosatetraenoic acid, contribute to this process. By revealing the mechanisms by which pyramidal cells lead to vasoconstriction, our findings shed light on the complex regulation of neurovascular coupling.