β‐Adrenergic receptors link NO/sGC/PKG signaling to BDNF expression during the consolidation of object recognition long‐term memory
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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Post-sample infusions of the β-adrenergic antagonist timolol into the hippocampal CA1 area disrupted long-term NOP memory in rats.
“Post-sample infusions of the β-adrenergic antagonist timolol into the hippocampal CA1 area disrupted long-term NOP memory in rats”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Furini et al., 2010
Object exploration elevated rat hippocampal BDNF levels.
“Object exploration elevated the rat hippocampal BDNF levels”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Furini et al., 2010
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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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