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

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Katalin Skrapits ◽  
Miklós Sárvári ◽  
Imre Farkas ◽  
Balázs Göcz ◽  
Szabolcs Takács ◽  
...  

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.

2021 ◽  
Author(s):  
Katalin Skrapits ◽  
Miklós Sárvári ◽  
Imre Farkas ◽  
Balázs Göcz ◽  
Szabolcs Takács ◽  
...  

Human reproduction is controlled by ~2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional 150-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Extrahypothalamic GnRH neurons were cholinergic. Though undetectable in adult rodents, the GnRH-GFP transgene was expressed transiently by caudate-putamen cholinergic interneurons in newborn transgenic mice. In slice electrophysiological studies, GnRH inhibited these interneurons via GnRHR1 autoreceptors. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen confirmed selective expression of GnRH and GnRHR1 autoreceptors in cholinergic cells 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. GnRH/GnRHR1 signaling as a potential therapeutic target in the treatment of neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson’s and Alzheimer’s diseases, needs to be explored.


1994 ◽  
Vol 339 (2) ◽  
pp. 269-287 ◽  
Author(s):  
P. A. Melrose ◽  
C. Pickel ◽  
H. S. Cheramie ◽  
W. G. Henk ◽  
M. A. Littlefield-Chabaud ◽  
...  

2020 ◽  
Author(s):  
Krishnakanth Kondabolu ◽  
Natalie M. Doig ◽  
Olaoluwa Ayeko ◽  
Bakhtawer Khan ◽  
Alexandra Torres ◽  
...  

AbstractThe striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomical evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum. To address this, we carried out monosynaptic retrograde tracing from genetically-defined populations of dorsal striatal neurons in adult male and female mice, quantifying the connectivity from STN neurons to spiny projection neurons, GABAergic interneurons, and cholinergic interneurons. In parallel, we used a combination of ex vivo electrophysiology and optogenetics to characterize the responses of a complementary range of dorsal striatal neuron types to activation of STN axons. Our tracing studies showed that the connectivity from STN neurons to striatal parvalbumin-expressing interneurons is significantly higher (~ four-to eight-fold) than that from STN to any of the four other striatal cell types examined. In agreement, our recording experiments showed that parvalbumin-expressing interneurons, but not the other cell types tested, commonly exhibited robust monosynaptic excitatory responses to subthalamostriatal inputs. Taken together, our data collectively demonstrate that the subthalamostriatal projection is highly selective for target cell type. We conclude that glutamatergic STN neurons are positioned to directly and powerfully influence striatal activity dynamics by virtue of their enriched innervation of GABAergic parvalbumin-expressing interneurons.


2000 ◽  
Vol 72 (5) ◽  
pp. 284-292 ◽  
Author(s):  
Keiichi Kawamoto ◽  
Susumu Tanaka ◽  
Masako Kawano ◽  
Toshiyuki Hayashi ◽  
Kimiyuki Tsuchiya

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