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• W2313020273 abstract "Abstract Transforming growth factor‐β signaling through intracellular Smad3 has been implicated in Parkinson's disease ( PD ) and it fulfills an important role in the neurogenesis and synaptic plasticity that occurs in the adult dentate gyrus ( DG ). The long‐term potentiation ( LTP ) induced in the DG by high‐frequency stimulation of the medial perforant pathway is abolished in the DG of Smad3‐deficient mice, but not in the CA 1 hippocampal region. Here, we show that NMDA ‐ and AMPA ‐type glutamate receptors do not participate in the inhibition of LTP associated with Smad3 deficiency. Moreover, there is no difference in the hippocampal GAD 65 and GAD 67 content, suggesting that GABA biosynthesis remains unaffected. Increased conductance and higher action potential firing thresholds were evident in intracellular recordings of granule cells from Smad3 deficient mice. Interestingly, phasic and tonic GABA A receptor ( GABA A R ) ‐ mediated neurotransmission is enhanced in the DG of Smad3‐deficient mice, and LTP induction can be rescued by inhibiting GABA A R with picrotoxin. Hence, Smad3 signaling in the DG appears to be necessary to induce LTP by regulating GABA A neurotransmission, suggesting a central role of this intracellular signaling pathway in the hippocampal brain plasticity related to learning and memory. image Smad3 deficient mice represent a new and interesting model of Parkinson's disease, displaying hippocampal dysfunctions that include decreased neurogenesis and the failure to induce LTP in the dentate gyrus. Here we show that Smad3 deficiency inhibits LTP induction by enhancing phasic and tonic GABA A receptor‐mediated neurotransmission, while LTP induction can be rescued with a GABA A receptor antagonist. Alteration of GABA neurotransmission is thought to produce hippocampal cognitive dysfunction in Down's syndrome or Alzheimer's disease, and here we provide new insights into the hippocampal changes in an animal model of Parkinson's disease." @default.
• W2313020273 created "2016-06-24" @default.
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• W2313020273 date "2016-02-18" @default.
• W2313020273 modified "2023-10-03" @default.
• W2313020273 title "Smad3 deficiency inhibits dentate gyrus LTP by enhancing GABA_A neurotransmission" @default.
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• W2313020273 doi "https://doi.org/10.1111/jnc.13558" @default.
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