Cited by 72Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchMemory Processes and Influences

β‐Adrenergic receptors link NO/sGC/PKG signaling to BDNF expression during the consolidation of object recognition long‐term memory

Furini, Cristiane R., Rossato, Janine I., Bitencourt, Lucas L., Medina, Jorge H., Izquierdo, Iván, Cammarota, Martín·2010·Hippocampus

Abstract

The nitric oxide (NO)/soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway is important for memory processing, but the identity of its downstream effectors as well as its actual participation in the consolidation of nonaversive declarative long-term memory (LTM) remain unknown. Here, we show that training rats in an object recognition (OR) learning task rapidly increased nitrites/nitrates (NOx) content in the CA1 region of the dorsal hippocampus while posttraining intra-CA1 microinfusion of the neuronal NO synthase (nNOS) inhibitor L-NN hindered OR LTM retention without affecting memory retrieval or other behavioral variables. The amnesic effect of L-NN was not state dependent, was mimicked by the sGC inhibitor LY83583 and the PKG inhibitor KT-5823, and reversed by coinfusion of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) and the PKG activator 8-bromoguanosine 3',5'-cyclic monophosphate (8Br-cGMP). SNAP did not affect the amnesic effect of LY83583 and KT-5823. Conversely, 8Br-cGMP overturned the amnesia induced by LY83583 but not that caused by KT-5823. Intra-CA1 infusion of the beta-adrenergic receptor blocker timolol right after training hindered OR LTM and, although coadministration of noradrenaline reversed the amnesia caused by L-NN, LY83583, and KT5823, the amnesic effect of timolol was unaffected by coinfusion of 8Br-cGMP or SNAP, indicating that hippocampal beta-adrenergic receptors act downstream NO/sGC/PKG signaling. We also found that posttraining intra-CA1 infusion of function-blocking anti-brain-derived neurotrophic factor (BDNF) antibodies hampered OR LTM retention, whereas OR training increased CA1 BDNF levels in a nNOS- and beta-adrenergic receptor-dependent manner. Taken together, our results demonstrate that NO/sGC/PKG signaling in the hippocampus is essential for OR memory consolidation and suggest that beta-adrenergic receptors link the activation of this pathway to BDNF expression during the consolidation of declarative memories.

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Crossref · 10.1002/hipo.20656

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Authors
Furini, C. R., Rossato, J. I., Bitencourt, L. L., Medina, J. H., Izquierdo, I., & Cammarota, M.
Affiliations
Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)
Venue
Hippocampus
Publisher
Wiley
Published
2009-06-16
Volume
20
Issue
5
Pages
672-683
ISSN
  • 1050-9631 (ISSN-L)
  • 1098-1063
OpenAlex
W2124007284
Cited by
72
References
101
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 5
FWCI
2.26
Type
journal article
Language
en
Open access
closed
Locations
  • Hippocampus (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
Keywords
nitric oxide, soluble guanylate cyclase, protein kinase G, beta-adrenergic receptors, brain-derived neurotrophic factor, object recognition memory, memory consolidation, CA1, neuronal nitric oxide synthase, L-NAME, timolol, norepinephrine, declarative memory
MeSH terms
Adrenergic beta-Antagonists, Animals, Antibodies, Behavior, Animal, Discrimination Learning, Dose-Response Relationship, Drug, Drug Interactions, Enzyme Inhibitors, Gene Expression Regulation, Guanylate Cyclase, Male, Nitric Oxide, Receptors, Adrenergic, beta, Time Factors, Timolol, Signal Transduction, Rats, Wistar, Cyclic GMP-Dependent Protein Kinases, Brain-Derived Neurotrophic Factor, Recognition, Psychology, Rats

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