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

Human reproduction is controlled by similar to 2000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here, we report the discovery and characterization of additional similar to 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.

Automated summary

The discovery of a large number of GnRH-synthesizing cells in the human basal ganglia and basal forebrain, expressing cholinergic markers, suggests a potential role of GnRH in non-reproductive functions in these regions. Further analysis revealed selective expression of GnRH and GnRHR1 autoreceptors in cholinergic cell populations, highlighting the complex molecular profile of these cells. The implications of GnRH/GnRHR1 signaling in neurodegenerative disorders affecting cholinergic neurocircuitries, such as Parkinson's and Alzheimer's diseases, require further exploration.