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

IF 4.2 3区医学 Q2 NEUROSCIENCES

Frontiers in Cellular Neuroscience Pub Date : 2025-02-19 eCollection Date: 2025-01-01 DOI:10.3389/fncel.2025.1531790

Olga Netsyk, Sergiy V Korol, Gunilla T Westermark, Bryndis Birnir, Zhe Jin

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引用次数: 0

Abstract

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 effect on neurotransmission in the hippocampus remains poorly understood. Here, we investigated the impact of non-amyloidogenic rodent IAPP (rIAPP) on GABA _A receptor-mediated neuronal inhibition in mouse dorsal and ventral hippocampal dentate gyrus (DG) granule cells. Using whole-cell patch-clamp recordings, we showed that rIAPP selectively enhanced both GABA-activated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in ventral, but not dorsal, hippocampal DG granule cells. The effect of rIAPP on sIPSCs was completely abolished in the presence of the amylin receptor antagonist IAPP_8-37. Interestingly, GABA _A 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 effect of rIAPP is likely associated with differential modulation of presynaptic GABA release as well as postsynaptic GABA _A receptors in the ventral as compared to the dorsal hippocampus. Our results suggest that rodent IAPP acts as a neuromodulator in hippocampal subregions by altering the strength of GABA _A receptor-mediated inhibitory signaling.

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来源期刊

Frontiers in Cellular Neuroscience NEUROSCIENCES-

CiteScore

7.90

自引率

3.80%

发文量

627

审稿时长

6-12 weeks

期刊介绍： Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.