Slow GABA transient and receptor desensitization shape synaptic responses evoked by hippocampal neurogliaform cells.
The kinetics of GABAergic synaptic currents can vary by an order of magnitude depending on the cell type. The neurogliaform cell (NGFC) has recently been identified as a key generator of slow GABA(A) receptor-mediated volume transmission in the isocortex. However, the mechanisms underlying slow GABA(A) receptor-mediated IPSCs and their use-dependent plasticity remain unknown. Here, we provide experimental and modeling data showing that hippocampal NGFCs generate an unusually prolonged (tens of milliseconds) but low-concentration (micromolar range) GABA transient, which is responsible for the slow response kinetics and which leads to a robust desensitization of postsynaptic GABA(A) receptors. This strongly contributes to the use-dependent synaptic depression elicited by various patterns of NGFC activity including the one detected during theta network oscillations in vivo. Synaptic depression mediated by NGFCs is likely to play an important modulatory role in the feedforward inhibition of CA1 pyramidal cells provided by the entorhinal cortex.
Karayannis
Theofanis
T
Medical Research Council Anatomical Neuropharmacology Unit, Mansfield Road, Oxford OX1 3TH, United Kingdom.
Elfant
David
D
Huerta-Ocampo
Icnelia
I
Teki
Sundeep
S
Scott
Ricardo S
RS
Rusakov
Dmitri A
DA
Jones
Mathew V
MV
Capogna
Marco
M
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D018728:Entorhinal Cortex / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D055366:Synaptic Potentials; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid