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BRIEF RESEARCH REPORT article

Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1531790

Rodent islet amyloid polypeptide (IAPP) selectively enhances GABAA-mediated neuronal inhibition in mouse ventral but not dorsal hippocampal dentate gyrus granule cells

Provisionally accepted
Olga Netsyk Olga Netsyk 1Sergiy V. Korol Sergiy V. Korol 1Gunilla T. Westermark Gunilla T. Westermark 1Bryndis Birnir Bryndis Birnir 1Zhe Jin Zhe Jin 2*
  • 1 Department of Medical Cell Biology, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden
  • 2 Neuroscience/Molecular physiology and Neuroscience, Uppsala University, Uppsala, Sweden

The final, formatted version of the article will be published soon.

    Islet amyloid polypeptide (IAPP, amylin) is a peptide hormone that plays an important role in glucose homeostasis but has been implicated in the pathophysiology of type 2 diabetes and Alzheimer's disease. However, its ebect on neurotransmission in the hippocampus remains poorly understood. Here, we investigated the impact of nonamyloidogenic rodent IAPP (rIAPP) on GABAA receptor-mediated neuronal inhibition in mouse dorsal and ventral hippocampal dentate gyrus (DG) granule cells. Using wholecell patch-clamp recordings, we showed that rIAPP selectively enhanced both GABAactivated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in ventral, but not dorsal, hippocampal DG granule cells. The ebect of rIAPP on sIPSCs was completely abolished in the presence of the amylin receptor antagonist IAPP8-37. Interestingly, GABAA receptor-mediated tonic current density remained unchanged in either dorsal or ventral hippocampal DG granule cells during rIAPP application. This region-specific and inhibition type-specific ebect of rIAPP is likely associated with diberential modulation of presynaptic GABA release as well as postsynaptic GABAA receptors in the ventral as compared to the dorsal hippocampus.Our results suggest that rodent IAPP acts as a neuromodulator in hippocampus subregions by altering the strength of GABAA receptor-mediated inhibitory signalling.

    Keywords: amylin, GABAA receptor, Hippocampus, Islet Amyloid Polypeptide, neuronal inhibition, Synaptic Transmission

    Received: 20 Nov 2024; Accepted: 20 Jan 2025.

    Copyright: © 2025 Netsyk, Korol, Westermark, Birnir and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhe Jin, Neuroscience/Molecular physiology and Neuroscience, Uppsala University, Uppsala, Sweden

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