Firing of hippocampal neurogliaform cells induces suppression of synaptic inhibition.
Little is known about how neuron firing recorded in vivo retrogradely influences synaptic strength. We injected the firing of a rat hippocampal neurogliaform cell (NGFC), a widely expressed GABAergic neuron type, detected in vivo during theta rhythm, into NGFCs of rat or neuronal nitric oxide synthase (nNOS)-Cre-tdTomato mouse recorded in vitro. We found that the "in vivo firing pattern" produced a transient firing-induced suppression of synaptic inhibition (FSI) evoked by a presynaptic NGFC. Imaging experiments demonstrate that FSI was associated with action potential backpropagation (bAP) and a supralinear increase in dendritic Ca(2+). The application of the L-type Ca(2+) channel antagonist nimodipine blocked FSI. Further pharmacological experiments, such as the application of a nitric oxide-sensitive guanylyl cyclase (NO-sGC) receptor antagonist, a NOS inhibitor, and NO donors, suggested that NO released from postsynaptic cells mediated FSI and likely activated presynaptic receptors to inhibit GABA release. The in vivo firing pattern modulated the size of unitary EPSPs impinging on NGFCs through FSI and not via a direct effect on excitatory synaptic transmission. Our data demonstrate: (1) retrograde signaling initiated by in vivo firing pattern, (2) interneuron bAPs detected with fast temporal resolution, and (3) a novel role for NO expressed by specific interneuron types.
Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford 0X1 3TH, United Kingdom; Inserm U836, Team 3, Grenoble Cedex 09, France, Université Joseph Fourier, Grenoble Institut des Neurosciences and Laboratoire Interdisciplinare de Physique, CNRS UMR 5588, Grenoble Cedex 09, France, and Laboratories of Excellence, Ion Channel Science and Therapeutics, Inserm U836, Grenoble Cedex 09, France.
Gengyu
G
Li
Robert
R
Stewart
Marco
M
Canepari
Marco
M
Capogna
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D018377:Neurotransmitter Agents; D009569:Nitric Oxide
hippocampus; imaging; interneuron; nitric oxide; retrograde messengers; synaptic transmission