The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia

Skrapits, Katalin and Sárvári, Miklós and Farkas, Imre and Göcz, Balázs and Takács, Szabolcs and Rumpler, Éva and Váczi, Viktória and Vastagh, Csaba and Rácz, Gergely and Matolcsy, András and Solymosi, Norbert and Póliska, Szilárd and Tóth, Blanka and Erdélyi, Ferenc and Szabó, Gábor and Giacobini, Paolo and Hrabovszky, Erik (2021) The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia. ELIFE, 10. pp. 1-26. ISSN 2050-084X

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Abstract

Human reproduction is controlled by ~2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional ~150,000-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Nearly all extrahypothalamic GnRH neurons expressed the cholinergic marker enzyme choline acetyltransferase. Similarly, hypothalamic GnRH neurons were also cholinergic both in embryonic and adult human brains. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen showed selective expression of GNRH1 and GNRHR1 autoreceptors in the cholinergic cell population and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher-order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. The role and changes of GnRH/GnRHR1 signaling in neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson's and Alzheimer's diseases, need to be explored.

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