Human-Specific Cortical Synaptic Connections and Their Plasticity: Is That What Makes Us Human?

Abstract

One outstanding difference between Homo sapiens and other mammals is the ability to perform highly complex cognitive tasks and behaviors, such as language, abstract thinking, and cultural diversity. How is this accomplished? According to one prominent theory, cognitive complexity is proportional to the repetition of specific computational modules over a large surface expansion of the cerebral cortex (neocortex). However, the human neocortex was shown to also possess unique features at the cellular and synaptic levels, raising the possibility that expanding the computational module is not the only mechanism underlying complex thinking. In a study published in PLOS Biology, Szegedi and colleagues analyzed a specific cortical circuit from live postoperative human tissue, showing that human-specific, very powerful excitatory connections between principal pyramidal neurons and inhibitory neurons are highly plastic. This suggests that exclusive plasticity of specific microcircuits might be considered among the mechanisms endowing the human neocortex with the ability to perform highly complex cognitive tasks.

Fig 1. Does cortical size matter?

This figure illustrates three major differences between cortices of two mammals: the mouse (widely used in neuroscience research) and Homo sapiens. A: Drawing of the cerebral hemispheres of a mouse (left) and a human (right) brain. The dark superficial region shows the neocortex, although it does not reflect actual cortical thickness. The brains are shown in the approximately same scale. Note the difference in size and convolutions between these two mammalian species, resulting in a ~1,000-fold increase in the human. This panel has been inspired by references [–20]. B: Oversimplified cortical circuit diagram. In red, excitatory pyramidal neurons are shown; in blue, two general subtypes of inhibitory interneurons are shown. C: Despite that the two circuits look identical, they may harbor different connectivity properties: As shown by Szegedi et al, the glutamatergic connections between pyramidal neurons (PNs) and the fast-spiking (FS) interneuron (here indicated as the light-blue cell), show major functional differences: they are much larger in humans, strong enough to trigger firing of the interneuron by one PN spike. In addition, the connection shows very robust activity-dependent synaptic plasticity.