Cited by 161Neuroscience and Neuropharmacology ResearchPhosphodiesterase function and regulationMemory and Neural Mechanisms

cGMP Signalling in the Mammalian Brain: Role in Synaptic Plasticity and Behaviour

Kleppisch, Thomas, Feil, Robert·2009·Handbook of Experimental Pharmacology

Abstract

The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays a crucial role in the control of cardiovascular and gastrointestinal homeostastis, but its effects on neuronal functions are less established. This review summarizes recent biochemical and functional data on the role of the cGMP signalling pathway in the mammalian brain, with a focus on the regulation of synaptic plasticity, learning, and other complex behaviours. Expression profiling, along with pharmacological and genetic manipulations, indicates important functions of nitric oxide (NO)-sensitive soluble guanylyl cyclases (sGCs), cGMP-dependent protein kinases (cGKs), and cGMP-regulated phosphodiesterases (PDEs) as generators, effectors, and modulators of cGMP signals in the brain, respectively. In addition, neuronal cGMP signalling can be transmitted through cyclic nucleotide-gated (CNG) or hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. The canonical NO/sGC/cGMP/cGK pathway modulates long-term changes of synaptic activity in the hippocampus, amygdala, cerebellum, and other brain regions, and contributes to distinct forms of learning and memory, such as fear conditioning, motor adaptation, and object recognition. Behavioural studies indicate that cGMP signalling is also involved in anxiety, addiction, and the pathogenesis of depression and schizophrenia. At the molecular level, different cGK isoforms appear to mediate effects of cGMP on presynaptic transmitter release and postsynaptic functions. The cGKs have been suggested to modulate cytoskeletal organization, vesicle and AMPA receptor trafficking, and gene expression via phosphorylation of various substrates including VASP, RhoA, RGS2, hSERT, GluR1, G-substrate, and DARPP-32. These and other components of the cGMP signalling cascade may be attractive new targets for the treatment of cognitive impairment, drug abuse, and psychiatric disorders.

Integrity signals

Registry

Crossref · 10.1007/978-3-540-68964-5_24

Cites

222 of 222 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • For inducible NOS to kill microbes, parasites, or cancer cells, high levels of NO are needed to destroy FeS centers and respiratory proteins in the target organism.

    “At the extreme of this spectrum, it is known that for inducible NOS to kill microbes, parasites, or cancer cells, high levels of NO are needed to destroy FeS centers and respiratory proteins in the target organism (28, 31, 32, 46).”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Kleppisch, T., & Feil, R.
Affiliations
  • Technical University of Munich (DE)
  • University of Tübingen (DE)
Corresponding author
Kleppisch, Thomas
Venue
Handbook of Experimental Pharmacology
Published
2009
Issue
191
Pages
549-579
ISSN
0171-2004 (ISSN-L)
OpenAlex
W190813598
Cited by
161
References
222
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 9 · 2020: 2 · 2019: 12 · 2018: 9 · 2017: 13 · 2016: 7 · 2015: 3 · 2014: 13 · 2013: 12 · 2012: 20
FWCI
15.46
Type
book chapter
Language
en
Open access
closed
Locations
  • Handbook of experimental pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
cGMP signaling, soluble guanylate cyclase, cGMP-dependent protein kinase, phosphodiesterase, nitric oxide, cyclic nucleotide-gated channels, HCN channels, synaptic plasticity, learning and memory, fear conditioning, anxiety, addiction, depression, schizophrenia, AMPA receptor trafficking, vesicle release, cytoskeletal organization, drug abuse, cognitive impairment, mental illness
MeSH terms
Animals, Brain, Gene Expression Regulation, Cyclic GMP, Humans, Synaptic Transmission, Neuronal Plasticity, Nitric Oxide, Signal Transduction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review