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Heparan Sulfates Regulate Axonal Excitability and Context Generalization through Ca2+/Calmodulin-Dependent Protein
Inseon Song1, Tatiana Kuznetsova2, David Baidoe-Ansah1
1Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
Cells
|March 11, 2023
Summary
Enzymatic removal of heparan sulfates impaired hippocampal neuron excitability and memory recall. Inhibiting CaMKII rescued these effects, revealing its role in heparan sulfate-mediated signaling.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Heparan sulfate proteoglycans (HSPGs) play crucial roles in neuronal function.
- Previous studies linked heparinase 1 treatment to impaired axonal excitability and memory deficits.
Purpose of the Study:
- To investigate the in vivo effects of heparinase 1 on hippocampal CA1 pyramidal neuron excitability and contextual memory.
- To elucidate the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in mediating these effects.
Main Methods:
- In vivo hippocampal CA1 injection of heparinase 1 in mice.
- Patch-clamp electrophysiology to assess neuronal excitability.
- Contextual fear conditioning and memory recall tests.
- Biochemical analysis of CaMKII activity and ankyrin G expression.
Main Results:
- Heparinase 1 injection increased CaMKII autophosphorylation and impaired action potential generation in CA1 neurons.
- Treatment led to context overgeneralization in memory recall tasks.
- Co-administration with a CaMKII inhibitor rescued neuronal excitability, ankyrin G expression, and contextual memory discrimination.
Conclusions:
- CaMKII is a key mediator of signaling downstream of heparan sulfate proteoglycans in hippocampal CA1 neurons.
- Impaired CA1 pyramidal cell excitability contributes to context generalization deficits during memory recall.
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