Department of Physiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.
Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Kraków, Poland.
Pharmacol Rep. 2024 Dec;76(6):1377-1389. doi: 10.1007/s43440-024-00674-6. Epub 2024 Nov 2.
The study examined the effects of 5-HT receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input.
Immunofluorescence imaging was performed using transverse hippocampal slices from transgenic mice expressing green fluorescent protein (GFP) under the Htr7 promoter. This was followed by whole-cell patch clamp electrophysiological recordings assessing the effects of pharmacologically activating 5-HT receptors on spontaneous inhibitory postsynaptic currents recorded from dentate granule cells and hilar mossy cells-two glutamatergic neuron types present in the dentate gyrus. Extracellular recordings of field excitatory postsynaptic potentials were then performed to assess whether 5-HT receptor activation influenced theta-burst stimulation-evoked plasticity of the perforant path synaptic input.
It was found that parvalbumin and somatostatin interneurons in the dentate gyrus expressed GFP, which suggests they express 5-HT receptors. However, activation of 5-HT receptors had no effect on GABAergic transmission targeting mossy cells or granule cells. There was also no effect of 5-HT receptor activation on perforant path plasticity either with intact or blocked GABA receptor signaling.
The presence of 5-HT receptors in a subset of parvalbumin and somatostatin interneurons in the mouse dentate gyrus could mean that they are involved in the inhibitory control of dentate gyrus activity. However, this potential effect was not evident in slice recordings of inhibitory transmission targeting principal cells and did not affect perforant path plasticity. Further experiments are needed to fully elucidate the functional role of these receptors in the dentate gyrus.
本研究考察了 5-HT 受体激活对齿状回 GABA 能传递和谷氨酸能穿通纤维输入处可塑性的影响。
使用在 Htr7 启动子控制下表达绿色荧光蛋白(GFP)的转基因小鼠的横切海马切片进行免疫荧光成像。然后进行全细胞膜片钳电生理记录,评估药理学激活 5-HT 受体对从齿状颗粒细胞和齿状回内的颗粒细胞和门区苔藓细胞(两种存在于齿状回的谷氨酸能神经元类型)记录的自发性抑制性突触后电流的影响。然后进行场兴奋性突触后电位的细胞外记录,以评估 5-HT 受体激活是否影响 theta 爆发刺激诱发的穿通纤维输入的可塑性。
发现齿状回中的 PV 和 SOM 中间神经元表达 GFP,这表明它们表达 5-HT 受体。然而,激活 5-HT 受体对靶向苔藓细胞或颗粒细胞的 GABA 能传递没有影响。5-HT 受体激活对穿通纤维可塑性也没有影响,无论是在 GABA 受体信号完整还是阻断的情况下。
在小鼠齿状回的一部分 PV 和 SOM 中间神经元中存在 5-HT 受体,这可能意味着它们参与了齿状回活动的抑制性控制。然而,这种潜在的影响在靶向主细胞的抑制性传递的切片记录中并不明显,也不影响穿通纤维的可塑性。需要进一步的实验来充分阐明这些受体在齿状回中的功能作用。