TY - JOUR
T1 - Group I mGluR-mediated activation of martinotti cells inhibits local cortical circuitry in human cortex
AU - Kroon, Tim
AU - Dawitz, Julia
AU - Kramvis, Ioannis
AU - Anink, Jasper
AU - Obermayer, Joshua
AU - Verhoog, Matthijs B.
AU - Wilbers, René
AU - Goriounova, Natalia A.
AU - Idema, Sander
AU - Baayen, Johannes C.
AU - Aronica, Eleonora
AU - Mansvelder, Huibert D.
AU - Meredith, Rhiannon M.
PY - 2019/7/16
Y1 - 2019/7/16
N2 - Group I metabotropic glutamate receptors (mGluRs) mediate a range of signaling and plasticity processes in the brain and are of growing importance as potential therapeutic targets in clinical trials for neuropsychiatric and neurodevelopmental disorders (NDDs). Fundamental knowledge regarding the functional effects of mGluRs upon pyramidal neurons and interneurons is derived largely from rodent brain, and their effects upon human neurons are predominantly untested. We therefore addressed how group I mGluRs affect microcircuits in human neocortex. We show that activation of group I mGluRs elicits action potential firing in Martinotti cells, which leads to increased synaptic inhibition onto neighboring neurons. Some other interneurons, including fast-spiking interneurons, are depolarized but do not fire action potentials in response to group I mGluR activation. Furthermore, we confirm the existence of group I mGluR-mediated depression of excitatory synapses in human pyramidal neurons. We propose that the strong increase in inhibition and depression of excitatory synapses onto layer 2/3 pyramidal neurons upon group I mGluR activation likely results in a shift in the balance between excitation and inhibition in the human cortical network.
AB - Group I metabotropic glutamate receptors (mGluRs) mediate a range of signaling and plasticity processes in the brain and are of growing importance as potential therapeutic targets in clinical trials for neuropsychiatric and neurodevelopmental disorders (NDDs). Fundamental knowledge regarding the functional effects of mGluRs upon pyramidal neurons and interneurons is derived largely from rodent brain, and their effects upon human neurons are predominantly untested. We therefore addressed how group I mGluRs affect microcircuits in human neocortex. We show that activation of group I mGluRs elicits action potential firing in Martinotti cells, which leads to increased synaptic inhibition onto neighboring neurons. Some other interneurons, including fast-spiking interneurons, are depolarized but do not fire action potentials in response to group I mGluR activation. Furthermore, we confirm the existence of group I mGluR-mediated depression of excitatory synapses in human pyramidal neurons. We propose that the strong increase in inhibition and depression of excitatory synapses onto layer 2/3 pyramidal neurons upon group I mGluR activation likely results in a shift in the balance between excitation and inhibition in the human cortical network.
KW - Fast-spiking interneuron
KW - Human cortex
KW - LTD
KW - MGluR
KW - Martinotti
KW - Single-cell RNA-sequencing
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UR - https://www.ncbi.nlm.nih.gov/pubmed/31354435
U2 - https://doi.org/10.3389/fncel.2019.00315
DO - https://doi.org/10.3389/fncel.2019.00315
M3 - Article
C2 - 31354435
SN - 1662-5102
VL - 13
JO - Frontiers in cellular neuroscience
JF - Frontiers in cellular neuroscience
M1 - 315
ER -