Elucidating the Structure and Function of Gonadotropin‐Releasing Hormone (GnRH) Neuron Dendrites

Iremonger, Karl J.; Herbison, Allan E.

doi:10.1002/9781118606803.ch12

Cited by 2 publications

(3 citation statements)

References 42 publications

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“…The Gnrh-cre (Tg[Gnrh1-cre]35Awo) mouse was generated by inserting a transgene that utilizes the mouse 3.4 Kb promoter to drive Cre recombinase expression in all GnRH neurons, in addition to some ectopic expression [26]. The Lhrh-cre (Tg[Gnrh1-cre]1Dlc) mouse, in which a mouse bacterial artificial chromosome containing the Gnrh1 gene driving Cre expression is inserted as a transgene into the genome, leads to Cre expression in ∼96% of the GnRH neurons, with very limited off-target expression [16, 27]. …”

Section: Introductionmentioning

confidence: 99%

Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice

et al. 2019

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There is an increasing trend in studies utilizing cell-specific deletion of genes through conditional gene deletion by CRE recombination. Despite numerous advantages, this strategy also has limitations such as ectopic CRE-expression and germline recombination. Two commonly used gonadotropin-releasing hormone (Gnrh)-driven CRE-expressing mice both target GnRH neurons. However, a direct comparison of the cells targeted and their phenotypic outcome have not yet been presented. To compare where recombination takes place, we crossed the Gnrh-cre and Lhrh-cre lines with the Rosa26-LacZ reporter mouse. Lhrh-cre allowed recombination of the Rosa26-LacZ gene in ∼700 cells, which is comparable to the GnRH neuronal population. Surprisingly, there were > 20 times more LacZ expressing cells in the adult Gnrh-cre:Rosa26-LacZ than the Lhrh-cre:Rosa26-LacZ brain. The greatest differences in targeting of the Gnrh-cre and Lhrh-cre lines were found in the septum, the suprachiasmatic nucleus, and the septohypothalamic area. This difference in cells targeted was present from embryonic day 12. A prior study using the Gnrh-cre to delete the transcription factor Otx2 found fewer GnRH neurons, leading to male and female subfertility. To recapitulate this study, we performed a fertility assay in Otx2:Lhrh-cre mice. We confirmed the requirement for Otx2 in GnRH neuron development, fertility and correct gonadotropin hormone release in Otx2:Lhrh-cre males, but the subfertility was more modest than in Otx2:Gnrh-cre and absent in female Otx2:Lhrh-cre. This suggests that ectopic expression of Gnrh-cre contributes to the reproductive phenotype observed. Finally, the Cre alleles caused germline recombination of the flox allele when transmitted from either parent, generating embryonic lethal knock-out offspring, producing smaller live litters.

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Section: Introductionmentioning

confidence: 99%

Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice

et al. 2019

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“…This is not only due to distance-related electrotonic decay of postsynaptic potentials, but also because these potentials have to travel through the large somatic compartment, which will act as a filter (41). Thus, synapses on the dendrite without the spike initiation zone may not have such strong effects on action potential generation, but rather impact more on controlling gene expression and the resting membrane potential of the cell (5,22,42). Interestingly though, regardless of which dendrite has the spike initiation zone, we find that over 90% of GnRH neurons have an Ankyrin G-bearing process heading in the direction of the ME.…”

Section: Action Potential Initiation In Gnrh Neuron Dendritesmentioning

confidence: 98%

“…Briefly, 200-m-thick coronal (for GnRH neurons around OVLT), sagittal (for MS and rPOA), or 400-m-thick ventral horizontal brain slices (for AHA/ME) were prepared (21,22) and GnRH neurons identified under fluorescence and a tight seal configuration (0.05-2 G⍀) was obtained using patch pipettes of 8 -12 M⍀ resistance (G150TF-3; Warner Instruments, Hamden, CT). The pipette solution (299 mosmol/kg, pH 7.3) contained (in mM) 135 K-gluconate, 5 NaCl, 10 HEPES, 10 EGTA, 1 MgCl 2 , 1 CaCl 2 , 5 MgATP, and 0.1 Na 2 GTP and 0.2% neurobiotin (SP-1120; Vector Laboratories, Burlingame, CA).…”

Section: Juxtacellular Filling Of Gnrh Neurons With Neurobiotin and Imentioning

confidence: 99%

Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice

Herde

Herbison

2015

Endocrinology

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GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

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Elucidating the Structure and Function of Gonadotropin‐Releasing Hormone (GnRH) Neuron Dendrites

Cited by 2 publications

References 42 publications

Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice

Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice

Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice

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