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Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex.

ABSTRACT: Activation of specific neural circuits in different layers of the primate dorsolateral prefrontal cortex (DLPFC) is essential for working memory, a core cognitive function. Recurrent excitation between pyramidal neurons in middle and deep layers of the DLPFC contributes to the laminar-specific activity associated with different working memory subprocesses. Excitation between cortical pyramidal neurons is mediated by glutamatergic synapses on dendritic spines, but whether the relative abundance of spines receiving cortical inputs differs between middle and deep cortical layers in human DLPFC is unknown. Additionally, GABAergic inputs to spines sculpt pyramidal neuron activity. Whether dendritic spines that receive a glutamatergic input from a cortical pyramidal neuron are targeted by GABAergic interneurons in the human DLPFC is unknown. Using triple-label fluorescence confocal microscopy, we found that 1) the density of spines receiving an input from a cortical pyramidal neuron is greater in the middle than in the deep laminar zone, 2) dendritic spines dually innervated by a cortical pyramidal neuron and an interneuron are present in the human DLPFC, and 3) the density of spines dually innervated by a cortical pyramidal neuron and an interneuron is also greater in the middle than in the deep laminar zone. Ultrastructural analyses support the presence of spines that receive a cortical pyramidal neuron synapse and an interneuron synapse in human and monkey DLPFC. These data support the notion that the DLPFC middle laminar zone is particularly endowed with a microcircuit structure that supports the gating, integrating and fine-tuning of synaptic information in recurrent excitatory microcircuits.

SUBMITTER: Glausier JR

PROVIDER: S-EPMC7770119 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We present detailed models of pyramidal cells from human neocortex, including models on their excitatory synapses, dendritic spines, dendritic NMDA- and somatic/axonal Na+ spikes that provided new insights into signal processing and computational capabilities of these principal cells. Six human layer 2 and layer 3 pyramidal cells (HL2/L3 PCs) were modeled, integrating detailed anatomical and physiological data from both fresh and postmortem tissues from human temporal cortex. The models predicted particularly large AMPA- and NMDA-conductances per synaptic contact (0.88 and 1.31 nS, respectively) and a steep dependence of the NMDA-conductance on voltage. These estimates were based on intracellular recordings from synaptically-connected HL2/L3 pairs, combined with extra-cellular current injections and use of synaptic blockers, and the assumption of five contacts per synaptic connection. A large dataset of high-resolution reconstructed HL2/L3 dendritic spines provided estimates for the EPSPs at the spine head (12.7 ± 4.6 mV), spine base (9.7 ± 5.0 mV), and soma (0.3 ± 0.1 mV), and for the spine neck resistance (50-80 M?). Matching the shape and firing pattern of experimental somatic Na+-spikes provided estimates for the density of the somatic/axonal excitable membrane ion channels, predicting that 134 ± 28 simultaneously activated HL2/L3-HL2/L3 synapses are required for generating (with 50% probability) a somatic Na+ spike. Dendritic NMDA spikes were triggered in the model when 20 ± 10 excitatory spinous synapses were simultaneously activated on individual dendritic branches. The particularly large number of basal dendrites in HL2/L3 PCs and the distinctive cable elongation of their terminals imply that ~25 NMDA-spikes could be generated independently and simultaneously in these cells, as compared to ~14 in L2/3 PCs from the rat somatosensory cortex. These multi-sites non-linear signals, together with the large (~30,000) excitatory synapses/cell, equip human L2/L3 PCs with enhanced computational capabilities. Our study provides the most comprehensive model of any human neuron to-date demonstrating the biophysical and computational distinctiveness of human cortical neurons.

Dataset Information

Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex.

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