Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA265

Poster Communications

Differential effects of insulin along the hippocampal dorsoventral axis on GABAAR-activated currents in mouse dentate gyrus granule cells and CA3 pyramidal neurons.

H. Hammoud1, O. Netsyk1, A. Tafreshiha1, S. V. Korol1, Z. Jin1, B. Birnir1

1. Department of Neuroscience, Uppsala university, Uppsala, Sweden.

The hippocampus is an acknowledged center for learning and memory. Besides the well-identified subregions Cornu Ammonis (CA) 1-3 and dentate gyrus (DG) of the hippocampus, increasing evidence suggests the existence of functional segregation along the hippocampal dorsoventral axis [1]. Insulin may influence neuronal transmission throughout the brain and alterations of the insulin signaling pathways may underlie the development of several neurodegenerative diseases [2]. GABA (γ-Aminobutyric acid) is the main neuroinhibitory transmitter and modulates neuronal excitability by binding to synaptic and extrasynaptic GABAA receptors (GABAAR) that mediate phasic and tonic currents, respectively [3]. Nevertheless, relatively little is still known about the effects of insulin on the GABAergic inhibitory currents in dorsal and ventral hippocampal primary neurons. GABAAR-mediated currents were recorded by the whole-cell patch-clamp technique in DG granule cells and CA3 pyramidal neurons from mouse dorsal (DH) and ventral (VH) hippocampal slices in the absence or presence of insulin (1 nM). Acute hippocampal slices (350 µm) were prepared from adult (8-12 weeks old) male C57BL/6J mice. Values are indicated as mean ± S.E.M., compared by two tails Student's t-test. In DG, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in granule cells was significantly higher in VH as compared to DH (DH: 0.8±0.12 Hz, n=45 vs. VH: 1.7±0.16 Hz, n=42, P <0.0001). Similarly, under the application of tetrodotoxin (TTX), a voltage-gated sodium channel blocker, the frequency of miniature inhibitory postsynaptic currents (mIPSCs) recorded from granule cells of VH was significantly higher as compared to DH (DH: 0.49±0.05 Hz, n=20 vs. VH: 0.85 ±0.11 Hz, n=14, P<0.001). In contrast, the frequency of only the mIPSCs but not the sIPSCs in CA3 neurons was higher in VH as compared to DH (DH: 1.8 ±0.2 Hz, n=11 vs. VH: 3.3 ±0.2 Hz, n=10, P<0.001). Application of insulin significantly increased the frequency of GABAAR-mediated synaptic currents of both sIPSCs and mIPSCs in DG granule cells from both DH and VH, (P<0.05) but insulin did not enhance the tonic current. In contrast, insulin potentiated GABA-mediated tonic current in CA3 neurons from both DH and VH, (P<0.05) but only significantly increased the mIPSCs in DH in these neurons (P<0.05). Thus, the results are consistent with postsynaptic mechanisms of the insulin effects in both DG granule cells and CA3 neurons. The results demonstrate distinct modes of GABAAR-mediated inhibition in the DG granule cells and CA3 pyramidal neurons along the dorsoventral axis of the hippocampus which can be differentially modulated by insulin.

Where applicable, experiments conform with Society ethical requirements