Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurons in rat neocortex.
Dual whole-cell recordings were made in layer 2/3 of the rat neocortex in synaptically connected pyramidal cells and fast-spiking non-accommodating (FSN) interneurons. In 75% of cell pairs (n = 80), the cells formed reciprocal synaptic connections. Trains of backpropagating action potentials in pyramidal cells induced Ca2+ transients in dendrites followed by inhibition of unitary IPSPs. IPSP depression was prevented by loading pyramidal cells with 5 mM BAPTA or EGTA. IPSP depression was mimicked by the metabotropic glutamate receptor (mGluR) agonist ACPD and was prevented by a mixture of the mGluR antagonists CPCCOEt and EGLU.IPSP depression was prevented by loading pyramidal cells with the antagonists of vesicular exocytosis botulinum toxin D (light chain) and GDP-beta-S. It is concluded that Ca2+-dependent release of a retrograde messenger, most probably glutamate, from pyramidal cell dendrites suppresses the inhibition of pyramidal neurons via activation of mGluRs located in FSN interneuron nerve terminals.
Zilberter
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Karolinska Institute, Department of Neuroscience, Division of Neuroanatomy and Brain Development, Berzelius v g 3, plan 5, S-17177 Stockholm, Sweden. yuri.zilberter@neuro.ki.se
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003712:Dendrites / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D018698:Glutamic Acid / Q000502:physiology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D007395:Interneurons / Q000502:physiology; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
D018094:Receptors, Metabotropic Glutamate; D013873:Thionucleotides; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D006153:Guanosine Diphosphate; C096325:botulinum toxin type D; D018698:Glutamic Acid; D004533:Egtazic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D001905:Botulinum Toxins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium