Involvement of nitric oxide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells during activation of cholinergic receptors

Judit K. Makara, I. Katona, G. Nyíri, Beáta Németh, Catherine Ledent, Masahiko Watanabe, Jan De Vente, T. Freund, Norbert Hájos

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Several types of neurons are able to regulate their synaptic inputs via releasing retrograde signal molecules, such as endocannabinoids or nitric oxide (NO). Here we show that, during activation of cholinergic receptors, retrograde signaling by NO controls CB1 cannabinoid receptor (CB 1R)-dependent depolarization-induced suppression of inhibition (DSI). Spontaneously occurring IPSCs were recorded in CA1 pyramidal neurons in the presence of carbachol, and DSI was induced by a 1-s-long depolarization step. We found that, in addition to the inhibition of CB1Rs, blocking the NO signaling pathway at various points also disrupted DSI. Inhibitors of NO synthase (NOS) or NO-sensitive guanylyl cyclase (NO-sGC) diminished DSI, whereas a cGMP analog or an NO donor inhibited IPSCs and partially occluded DSI in a CB1R-dependent manner. Furthermore, an NO scavenger applied extracellularly or postsynaptically also decreased DSI, whereas L-arginine, the precursor for NO, prolonged it. DSI of electrically evoked IPSCs was also blocked by an inhibitor of NOS in the presence, but not in the absence, of carbachol. In line with our electrophysiological data, double immunohistochemical staining revealed an NO-donor-induced cGMP accumulation in CB1R-positive axon terminals. Using electron microscopy,we demonstrated the postsynaptic localization of neuronal NOS at symmetrical synapses formed by CB1R-positive axon terminals on pyramidal cell bodies, whereas NO-sGC was found in the presynaptic terminals. These electrophysiological and anatomical results in the hippocampus suggest that NO is involved in depolarization-induced CB1R-mediated suppression of IPSCs as a retrograde signal molecule and that operation of this cascade is conditional on cholinergic receptor activation.

Original languageEnglish
Pages (from-to)10211-10222
Number of pages12
JournalJournal of Neuroscience
Volume27
Issue number38
DOIs
Publication statusPublished - Sep 19 2007

Fingerprint

Pyramidal Cells
Cholinergic Receptors
Nitric Oxide
Presynaptic Terminals
Nitric Oxide Synthase
Nitric Oxide Donors
Carbachol
Cannabinoid Receptor CB1
Endocannabinoids
Synapses
Arginine
Hippocampus
Electron Microscopy
Staining and Labeling
Neurons

Keywords

  • CB receptor
  • cGMP
  • GABA
  • Hippocampus
  • Retrograde
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Involvement of nitric oxide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells during activation of cholinergic receptors. / Makara, Judit K.; Katona, I.; Nyíri, G.; Németh, Beáta; Ledent, Catherine; Watanabe, Masahiko; De Vente, Jan; Freund, T.; Hájos, Norbert.

In: Journal of Neuroscience, Vol. 27, No. 38, 19.09.2007, p. 10211-10222.

Research output: Contribution to journalArticle

Makara, Judit K. ; Katona, I. ; Nyíri, G. ; Németh, Beáta ; Ledent, Catherine ; Watanabe, Masahiko ; De Vente, Jan ; Freund, T. ; Hájos, Norbert. / Involvement of nitric oxide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells during activation of cholinergic receptors. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 38. pp. 10211-10222.
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AU - Makara, Judit K.

AU - Katona, I.

AU - Nyíri, G.

AU - Németh, Beáta

AU - Ledent, Catherine

AU - Watanabe, Masahiko

AU - De Vente, Jan

AU - Freund, T.

AU - Hájos, Norbert

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