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

PLoS Biol. 2016 Nov 9;14(11):e2000237. doi: 10.1371/journal.pbio.2000237. eCollection 2016 Nov.

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.

MeSH terms

  • Axons / physiology*
  • Glutamic Acid / metabolism*
  • Humans
  • Interneurons / metabolism*
  • Long-Term Synaptic Depression
  • Neocortex / physiology*
  • Neuronal Plasticity / physiology*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Glutamic Acid
  • gamma-Aminobutyric Acid

Grant support

Medical Research council UK. Received by KL (MRC Anatomical Neuropharmacology Unit Senior Scientist). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ERC INTERIMPACT project (ERC-2010-AdG). Received by GT. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. National Brain Research (Nemzeti Agykutatási) program agykutatas.com. Received by KL (KTIA_NAP_13-2-2015-0005), GM (KTIA_13_NAP-A-I/16) and GT. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Hungarian Academy of Sciences, the Hungarian National Office for Research and Technology (GINOP-2.3.2-15-2016-00018), the National Research Development and Innovation Office of Hungary (VKSZ-14-1-2015-0155). Received by GT. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.