Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex

Abstract

Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry. We find that local connectivity is comparable with mouse layer 2/3 connections in the anatomical homologue (temporal association area), but synaptic connections in human are 3-fold stronger and more reliable (0% vs 25% failure rates, respectively). We developed a theoretical approach to quantify properties of spinous synapses showing that synaptic conductance and voltage change in human dendritic spines are 3–4-folds larger compared with mouse, leading to significant NMDA receptor activation in human unitary connections. This model prediction was validated experimentally by showing that NMDA receptor activation increases the amplitude and prolongs decay of unitary excitatory postsynaptic potentials in human but not in mouse connections. Since NMDA-dependent recurrent excitation facilitates persistent activity (supporting working memory), our data uncovers cortical microcircuit properties in human that may contribute to language processing in MTG.

Cellular and Synaptic Diversity of Layer 2-3 Pyramidal Neurons in Human Individuals

“…This skewed distribution of synaptic amplitudes has been observed across cortical layers and areas 30–33 , and large-amplitude synapses brought about by plasticity may underlie the coactivation of groups of neurons thought to be fundamental for computations of the brain 34–36 . The median amplitude of 0.46 mV is within the range of previous human studies 9,10,12,14,37 . Similar to EPSP amplitude, the PPR showed a skewed distribution (Figure 3E-F).…”

“…In human studies it is especially challenging to derive general principles considering the differences in genetic and environmental backgrounds and their influence on functional properties of the neurons 18–20 . Previous studies on human neuronal and synaptic function relied on electrophysiological approaches with a limited number of samples from each individual 4,5,9,10,12,14,18,20–23 , requiring pooling across many different individuals. Thus, generalization of cortical microcircuit properties is still limited by the unresolved contributions of within- and between-individual differences to functional heterogeneity.…”

Evolution of cortical neurons supporting human cognition

“…These findings were recently confirmed in several connectivity studies investigating connected pairs of neurons in mouse and human [68][69][70]. L2/L3 excitatory connections were stronger and more reliable in humans, with fast recovery from depression [68,70].…”

Accelerated signal propagation speed in human neocortical microcircuits

“…To account for the surface area of spines, we used the spine correction factor (F) of 1.9 and 1.5 for human and rat PCs, respectively, by multiplying C m and dividing R m by F in segments which are at a distance of at least 60 mm from the soma ( 25, 74 ). In this study we did not attempt to fit the nonlinear effect of Ih of the voltage response of the cells.…”