ArticlePflugers Archiv : European journal of physiology2025
Inhibition of Rho-kinase by fasudil contributes to the modulation of the synaptic plasticity response in the rat hippocampus.
Article in Pflugers Archiv : European journal of physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Metaplasticity refers to an activity-dependent change in the physiological or biochemical state of neurons that changes their ability to generate subsequently induced synaptic plasticity, such as long-term potentiation (LTP) or long-term depression (LTD). Rho-kinases (ROCK) are known to be important for stable changes in synaptic strength, especially LTP. In this study, we investigated whether LTP inhibition in synapses primed with 1-Hz stimulation was affected by ROCK inhibition in young adult male rats. The study also examined the pattern of tau phosphorylation that occurs during metaplastic regulation, applying into perspective the phosphorylation of tau protein by ROCK. Field potentials consisting of an excitatory postsynaptic potential (fEPSP) and population spike (PS) were recorded from the granule cell layer of the hippocampal dentate gyrus (DG). Metaplastic LTP was induced by strong tetanic stimulation (HFS) of the lateral perforant path after a low-frequency stimulation (LFS) protocol. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record fEPSP and drug infusion. Drug infusion (saline, n = 8; fasudil, n = 8, 10 µM) was started after the 15-min baseline recording and lasted for 60 min. Total and phosphorylated tau levels were measured in the stimulated hippocampus, which was immediately removed after the electrophysiological recording. LFS prevented the induction of LTP in response to HFS and even produced synaptic LTD in the saline-infused group (83.8 ± 2.6% of the baseline), but moderate potentiation of fEPSP (121.1 ± 7.7% of the baseline) occurred at the end of recording in the experiments where fasudil infusion was performed. LFS caused a comparable early depression, and HFS resulted in a comparable potentiation of the PS amplitude in both groups. Granular cells of the DG failed to exhibit synaptic LTP inhibition in the presence of fasudil, and levels of total and phosphorylated GSK-3β and levels of phosphorylated tau (Ser
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