AMPA receptor channels with long-lasting desensitization in bipolar interneurons contribute to synaptic depression in a novel feedback circuit in layer 2/3 of rat neocortex.
A novel, local inhibitory circuit in layer 2/3 of rat somatosensory cortex is described that connects pyramidal cells reciprocally with GABAergic vasoactive intestinal polypeptide-immunoreactive bipolar interneurons. In paired whole-cell recordings, the glutamatergic unitary responses (EPSPs or EPSCs) in bipolar cells evoked by repetitive (10 Hz) stimulation of a pyramidal cell show strong frequency-dependent depression. Unitary IPSPs evoked in pyramidal cells by repetitive stimulation of bipolar cells, on average, maintained their amplitude. This suggests that the excitatory synapses on bipolar cells act as a low-pass filter in the reciprocal pyramid-to-bipolar circuit. The EPSCs in bipolar cells are mediated predominantly by AMPA receptor (AMPAR) channels. AMPARs desensitize rapidly and recover slowly from desensitization evoked by a brief pulse of glutamate. In slices, reduction of AMPAR desensitization by cyclothiazide (50-100 microm) or conditioning steady-state desensitization induced by application of extracellular AMPA (50 nm) or glutamate (50 microm) strongly reduced synaptic depression. It is concluded that in the local circuits between pyramidal and bipolar cells the desensitization of AMPARs in bipolar cells contributes to low-pass feedback inhibition of layer 2/3 pyramidal neurons by bipolar cells.
Rozov
A
A
Abt. Zellphysiologie and Abteilung Molekulare Neurobiologie, Max-Planck-Institut für medizinische Forschung, D-69120 Heidelberg, Germany.
Jerecic
J
J
Sakmann
B
B
Burnashev
N
N
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001581:Benzothiadiazines / Q000494:pharmacology; D003712:Dendrites / Q000648:ultrastructure; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005246:Feedback / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007473:Ion Channels / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001581:Benzothiadiazines; D007473:Ion Channels; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D005680:gamma-Aminobutyric Acid; C013411:biocytin; D008239:Lysine; C004639:cyclothiazide