Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex.

Viktor Szegedi,Karri Lamsa,Eszter Csakvari,Melinda Paizs,Gabor Tamas,Gabor Molnar,Pal Barzo,Alberto Bacci

doi:10.1371/journal.pbio.2000237

Abstract

In the human neocortex, single excitatory pyramidal cells can elicit very large glutamatergic EPSPs (VLEs) in inhibitory GABAergic interneurons capable of triggering their firing with short (3–5 ms) delay. Similar strong excitatory connections between two individual neurons have not been found in nonhuman cortices, suggesting that these synapses are specific to human interneurons. The VLEs are crucial for generating neocortical complex events, observed as single pyramidal cell spike-evoked discharge of cell assemblies in the frontal and temporal cortices. However, long-term plasticity of the VLE connections and how the plasticity modulates neocortical complex events has not been studied. Using triple and dual whole-cell recordings from synaptically connected human neocortical layers 2–3 neurons, we show that VLEs in fast-spiking GABAergic interneurons exhibit robust activity-induced long-term depression (LTD). The LTD by single pyramidal cell 40 Hz spike bursts is specific to connections with VLEs, requires group I metabotropic glutamate receptors, and has a presynaptic mechanism. The LTD of VLE connections alters suprathreshold activation of interneurons in the complex events suppressing the discharge of fast-spiking GABAergic cells. The VLEs triggering the complex events may contribute to cognitive processes in the human neocortex, and their long-term plasticity can alter the discharging cortical cell assemblies by learning.

Highlights

Evolution has shaped the human neocortex producing microcircuit features that are specific to our species [1]
By performing triple and dual whole-cell recordings of synaptically connected identified neurons, we found that very large glutamatergic EPSP (VLE) exhibit metabotropic glutamate receptor-dependent long-term depression (LTD) that converts them to common weak excitatory postsynaptic potential (EPSP) connections
By performing triple and dual whole-cell recordings from identified layers 2–3 (L2–3) human neocortical neurons, we found that some fast-spiking GABAergic interneurons (FSINs) receive glutamatergic input from individual afferent pyramidal cell (PC) showing VLEs (Fig 1A and 1B)

Summary

Introduction

Evolution has shaped the human neocortex producing microcircuit features that are specific to our species [1]. It has been proposed that the VLEs and the complex events participate in cortical information encoding in high order cognitive processes [10] This would predict that these events are dynamically modulated by learning [14,15]. We hypothesize that the immense strength of VLEs is generated and regulated by common activity-driven synaptic long-term plasticity processes, and that they may occur in various different inhibitory interneuron types [16,17]. These connections could be hardwired selectively in a specific, yet unknown, subset of postsynaptic GABAergic interneurons without prominent lasting plasticity in the adult neocortex [18,19]

Methods

Results

Discussion

Conclusion