Insulin modulates hippocampal activity‐dependent synaptic plasticity in a N‐methyl‐d‐aspartate receptor and phosphatidyl‐inositol‐3‐kinase‐dependent manner
Open accessAbstract
Insulin and its receptor are both present in the central nervous system and are implicated in neuronal survival and hippocampal synaptic plasticity. Here we show that insulin activates phosphatidylinositol 3‐kinase (PI3K) and protein kinase B (PKB), and results in an induction of long‐term depression (LTD) in hippocampal CA1 neurones. Evaluation of the frequency–response curve of synaptic plasticity revealed that insulin induced LTD at 0.033 Hz and LTP at 10 Hz, whereas in the absence of insulin, 1 Hz induced LTD and 100 Hz induced LTP. LTD induction in the presence of insulin required low frequency synaptic stimulation (0.033 Hz) and blockade of GABAergic transmission. The LTD or LTP induced in the presence of insulin was N‐methyl‐d‐aspartate (NMDA) receptor specific as it could be inhibited by α‐amino‐5‐phosphonopentanoic acid (APV), a specific NMDA receptor antagonist. LTD induction was also facilitated by lowering the extracellular Mg 2+ concentration, indicating an involvement of NMDA receptors. Inhibition of PI3K signalling or discontinuing synaptic stimulation also prevented this LTD. These results show that insulin modulates activity‐dependent synaptic plasticity, which requires activation of NMDA receptors and the PI3K pathway. The results obtained provide a mechanistic link between insulin and synaptic plasticity, and explain how insulin functions as a neuromodulator.
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Insulin is involved in activity-dependent processes of synaptic plasticity, namely long-term potentiation and long-term depression.
“It is also involved in activity-dependent processes of synaptic plasticity (ie, long-term potentiation [LTP] and long-term depression [LTD]).118”
From Intranasal insulin (2021) · cites this paper as [118]
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- Authors
- Van Der Heide, L. P., Kamal, A., Artola, A., Gispen, W. H., & Ramakers, G. M. J.
- Affiliations
- University Medical Center Utrecht (NL)
- University of Antwerp (BE)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2005-06-30
- Volume
- 94
- Issue
- 4
- Pages
- 1158-1166
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1563190123
- Cited by
- 278
- References
- 53
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 15 · 2023: 21 · 2022: 13 · 2021: 26 · 2020: 13 · 2019: 17 · 2018: 15 · 2017: 5 · 2016: 10 · 2015: 13 · 2014: 15 · 2013: 13 · 2012: 12
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- insulin, hippocampus, synaptic plasticity, long-term depression, long-term potentiation, NMDA receptor, phosphatidylinositol 3-kinase, Akt, CA1 neurons, GABAergic neurotransmission, magnesium, neuromodulation, insulin receptor
- MeSH terms
- Animals, Electric Stimulation, Enzyme Activation, Hippocampus, Insulin, Male, Neuronal Plasticity, Neurons, Proto-Oncogene Proteins, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Protein Serine-Threonine Kinases, Neurotransmitter Agents, Phosphatidylinositol 3-Kinases, Long-Term Synaptic Depression, Proto-Oncogene Proteins c-akt, Rats, In Vitro Techniques
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