Different dendritic domains of the GnRH neuron underlie the pulse and surge modes of GnRH secretion in female mice

The gonadotropin-releasing hormone (GnRH) neurons exhibit pulse and surge modes of activity to control fertility. They also exhibit an unusual bipolar morphology comprised of a classical soma-proximal dendritic zone and an elongated secretory process that can operate as both a dendrite and an axon, termed a ‘dendron’. We show using expansion microscopy that the highest density of synaptic inputs to a GnRH neuron exists at its distal dendron. In vivo, selective chemogenetic inhibition of the GnRH neuron distal dendron abolishes the luteinizing hormone (LH) surge and markedly dampens LH pulses. In contrast, inhibitory chemogenetic and optogenetic strategies targeting the GnRH neuron soma-proximal dendritic zone abolish the LH surge but have no effect upon LH pulsatility. These observations indicate that electrical activity at the soma-proximal dendrites of the GnRH neuron is only essential for the LH surge while the distal dendron represents an autonomous zone where synaptic integration drives pulsatile GnRH secretion.

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Extraction of Synaptic Input Properties in Vivo

Neural Computation ◽

10.1162/neco_a_00975 ◽

2017 ◽

Vol 29 (7) ◽

pp. 1745-1768 ◽

Cited By ~ 3

Author(s):

Paolo Puggioni ◽

Marta Jelitai ◽

Ian Duguid ◽

Mark C.W. van Rossum

Keyword(s):

Voltage Clamp ◽

Synaptic Input ◽

Event Rate ◽

Synaptic Integration ◽

Neural Function ◽

State Change ◽

Input Rate ◽

Time Constants ◽

Synaptic Inputs

Knowledge of synaptic input is crucial for understanding synaptic integration and ultimately neural function. However, in vivo, the rates at which synaptic inputs arrive are high, so that it is typically impossible to detect single events. We show here that it is nevertheless possible to extract the properties of the events and, in particular, to extract the event rate, the synaptic time constants, and the properties of the event size distribution from in vivo voltage-clamp recordings. Applied to cerebellar interneurons, our method reveals that the synaptic input rate increases from 600 Hz during rest to 1000 Hz during locomotion, while the amplitude and shape of the synaptic events are unaffected by this state change. This method thus complements existing methods to measure neural function in vivo.

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Complete Kisspeptin Receptor Inactivation Does Not Impede Exogenous GnRH-Induced LH Surge in Humans

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-00410 ◽

2018 ◽

Vol 103 (12) ◽

pp. 4482-4490 ◽

Cited By ~ 2

Author(s):

Justine Hugon-Rodin ◽

Keisuke Yoshii ◽

Najiba Lahlou ◽

Jennifer Flandrin ◽

Anne Gompel ◽

...

Keyword(s):

Transmembrane Domain ◽

Hypogonadotropic Hypogonadism ◽

Pulse Therapy ◽

Breast Development ◽

Primary Amenorrhea ◽

Lh Surge ◽

Transfected Cells ◽

Pulsatile Gnrh ◽

Gnrh Therapy

Abstract Context Mutations in the kisspeptin receptor (KISS1R) gene have been reported in a few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). Objectives To describe a female patient with nCHH and a novel homozygous KISS1R mutation and to assess the role of kisspeptin pathway to induce an ovulation by GnRH pulse therapy. Design, Setting, and Intervention Observational study of a patient including genetic and kisspeptin receptor functions and treatment efficiency using a GnRH pump. Main Outcome Measure Response to pulsatile GnRH therapy Results A partial isolated gonadotropic deficiency was diagnosed in a 28-year-old woman with primary amenorrhea and no breast development. A novel homozygous c.953T>C variant was identified in KISS1R. This mutation led to substitution of leucine 318 for proline (p.Leu318Pro) in the seventh transmembrane domain of KISS1R. Signaling via the mutated receptor was profoundly impaired in HEK293-transfected cells. The mutated receptor was not detected on the membrane of HEK293-transfected cells. After several pulsatile GnRH therapy cycles, an LH surge with ovulation and pregnancy was obtained. Conclusion GnRH pulsatile therapy can induce an LH surge in a woman with a mutated KISS1R, which was previously thought to be completely inactivated in vivo.

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GnRH Neuron-Specific Ablation of G q/11 Results in Only Partial Inactivation of the Neuroendocrine-Reproductive Axis in Both Male and Female Mice: In Vivo Evidence for Kiss1r-Coupled G q/11-Independent GnRH Secretion

Journal of Neuroscience ◽

10.1523/jneurosci.0041-15.2015 ◽

2015 ◽

Vol 35 (37) ◽

pp. 12903-12916 ◽

Cited By ~ 15

Author(s):

A. V. Babwah ◽

V. M. Navarro ◽

M. Ahow ◽

M. Pampillo ◽

C. Nash ◽

...

Keyword(s):

Gnrh Neuron ◽

Male And Female ◽

Gnrh Secretion ◽

Female Mice ◽

Reproductive Axis ◽

Partial Inactivation

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A T.E.M. study of mouse mammary epithelial cell secretory differentiation cultured on collagen and Matrigel

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100085241 ◽

1991 ◽

Vol 49 ◽

pp. 188-189

Author(s):

W.N. Bentham ◽

V. Rocha

Keyword(s):

Cell Culture ◽

Mammary Epithelial ◽

Secretory Process ◽

Cell Culture System ◽

Protein Maturation ◽

Cell Culture Techniques ◽

Culture Techniques ◽

Mouse Mammary Epithelial Cell ◽

Secretory Differentiation

It has been an interest of our lab to develop a mammary epethelial cell culture system that faithfully duplicates the in vivo condition of the lactating gland. Since the introduction of collagen as a matrix on which cells are cultivated other E.C.M. type matrices have been made available and are used in many cell culture techniques. We have previously demonstrated that cells cultured on collagen and Matrigel do not differentiate as they do in vivo. It seems that these cultures often produce cells that show a disruption in the secretory process. The appearance of large ribosomal studded vesicles, that specifically label with antibody to casein, suggest an interruption of both protein maturation and secretion at the E.R. to golgi transition. In this report we have examined cultures on collagen and Matrigel at relative high and low seeding densities and compared them to cells from the in vivo condition.

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Pulsatile GnRH secretion from primary cultures of sheep olfactory placode explants

Reproduction ◽

10.1530/reprod/120.2.391 ◽

2000 ◽

pp. 391-396 ◽

Cited By ~ 11

Author(s):

AH Duittoz ◽

M Batailler

Keyword(s):

Culture Medium ◽

Primary Cultures ◽

Pulsatile Secretion ◽

Olfactory Placode ◽

Gnrh Secretion ◽

Individual Culture ◽

Pulsatile Gnrh

The aim of this study was to investigate the development of pulsatile GnRH secretion by GnRH neurones in primary cultures of olfactory placodes from ovine embryos. Culture medium was collected every 10 min for 8 h to detect pulsatile secretion. In the first experiment, pulsatile secretion was studied in two different sets of cultures after 17 and 24 days in vitro. In the second experiment, a set of cultures was tested after 10, 17 and 24 days in vitro to investigate the development of pulsatile GnRH secretion in each individual culture. This study demonstrated that (i) primary cultures of GnRH neurones from olfactory explants secreted GnRH in a pulsatile manner and that the frequency and mean interpulse duration were similar to those reported in castrated ewes, and (ii) pulsatile secretion was not present at the beginning of the culture but was observed between 17 and 24 days in vitro, indicating the maturation of individual neurones and the development of their synchronization.

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Calcium secretion in canine tracheal mucosa

Journal of Applied Physiology ◽

10.1152/jappl.1985.59.4.1191 ◽

1985 ◽

Vol 59 (4) ◽

pp. 1191-1195 ◽

Cited By ~ 2

Author(s):

F. J. Al-Bazzaz ◽

T. Jayaram

Keyword(s):

Short Circuit ◽

Short Circuit Current ◽

Open Circuit ◽

Potential Difference ◽

Secretory Process ◽

Metabolic Inhibitor ◽

Tracheal Mucosa ◽

Transepithelial Potential ◽

Transepithelial Potential Difference

Calcium (Ca) affects many cellular functions of the respiratory tract mucosa and might alter the viscoelastic properties of mucus. To evaluate Ca homeostasis in a respiratory epithelium we investigated transport of Ca by the canine tracheal mucosa. Mucosal tissues were mounted in Ussing-type chambers and bathed with Krebs-Henseleit solution at 37 degrees C. Unidirectional fluxes of 45Ca were determined in tissues that were matched by conductance and short-circuit current (SCC). Under short-circuit conditions there was a significant net Ca secretion of 1.82 +/- 0.36 neq . cm-2 . h-1 (mean +/- SE). Under open-circuit conditions, where the spontaneous transepithelial potential difference could attract Ca toward the lumen, net Ca secretion increased significantly to 4.40 +/- 1.14 compared with 1.54 +/- 1.17 neq . cm-2 . h-1 when the preparation was short-circuited. Addition of a metabolic inhibitor, 2,4-dinitrophenol (2 mM in the mucosal bath), decreased tissue conductance and SCC and slightly decreased the unidirectional movement of Ca from submucosa to lumen. Submucosal epinephrine (10 microM) significantly enhanced Ca secretion by 2.0 +/- 0.63 neq . cm-2 . h-1. Submucosal ouabain (0.1 mM) failed to inhibit Ca secretion. The data suggest that canine tracheal mucosa secretes Ca; this secretory process is augmented by epinephrine or by the presence of a transepithelial potential difference as found under in vivo conditions.

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Active membrane conductances and morphology of a collision detection neuron broaden its impedance profile and improve membrane synchrony

10.1101/454702 ◽

2018 ◽

Author(s):

Richard Dewell ◽

Fabrizio Gabbiani

Keyword(s):

Synaptic Input ◽

Collision Detection ◽

Dendritic Morphology ◽

Synaptic Integration ◽

Neuronal Membrane ◽

Hcn Channels ◽

Movement Detector ◽

Membrane Impedance ◽

Wide Range

Brains processes information through the coordinated efforts of billions of individual neurons, each encoding a small part of the overall information stream. Central to this is how neurons integrate and transform complex patterns of synaptic inputs. The neuronal membrane impedance sets the gain and timing for synaptic integration, determining a neuron's ability to discriminate between synaptic input patterns. Using single and dual dendritic recordings in vivo, pharmacology, and computational modeling, we characterized the membrane impedance of a collision detection neuron in the grasshopper, Schistocerca americana. We examined how the cellular properties of the lobula giant movement detector (LGMD) neuron are tuned to enable the discrimination of synaptic input patterns key to its role in collision detection. We found that two common active conductances gH and gM, mediated respectively by hyperpolarization-activated cyclic nucleotide gated (HCN) channels and by muscarine sensitive M-type K+ channels, promote broadband integration with high temporal precision over the LGMD's natural range of membrane potentials and synaptic input frequencies. Additionally, we found that the LGMD's branching morphology increased the gain and decreased delays associated with the mapping of synaptic input currents to membrane potential. We investigated whether other branching dendritic morphologies fulfill a similar function and found this to be true for a wide range of morphologies, including those of neocortical pyramidal neurons and cerebellar Purkinje cells. These findings further our understanding of the integration properties of individual neurons by showing the unexpected role played by two widespread active conductances and by dendritic morphology in shaping synaptic integration.

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