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bioRxiv · 10.1101/2024.09.17.613425

Activation of 5-HT7 receptors in the mouse dentate gyrus selectively enhances GABAergic inhibition of hilar mossy cells without affecting plasticity at the perforant path synapse

Siwiec, M.·Bobula, B.·Kielbinski, M.·Multan, N.·Hess, G.·Tokarski, K.
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Abstract

BackgroundThe study examined the effects of 5-HT7 receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input. MethodsImmunofluorescence 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-HT7 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-HT7 receptor activation influenced theta-burst stimulation-evoked plasticity of the perforant path synaptic input. ResultsIt was found that parvalbumin and somatostatin interneurons in the dentate gyrus expressed GFP, which suggests they express 5-HT7 receptors. However, activation of 5-HT7 receptors had no effect on GABAergic transmission targeting mossy cells or granule cells. There was also no effect of 5-HT7 receptor activation on perforant path plasticity either with intact or blocked GABAA receptor signaling. ConclusionThe presence of 5-HT7 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.

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Siwiec, M., Bobula, B., Kielbinski, M., Multan, N., Hess, G., Tokarski, K.. 2024-09-17. Activation of 5-HT7 receptors in the mouse dentate gyrus selectively enhances GABAergic inhibition of hilar mossy cells without affecting plasticity at the perforant path synapse. https://doi.org/10.1101/2024.09.17.613425

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