DynPeak: An Algorithm for Pulse Detection and Frequency Analysis in Hormonal Time Series

Vidal, Alexandre; Zhang, Qinghua; Médigue, Claire; Fabre, Stéphane; Clément, Frédérique

doi:10.1371/journal.pone.0039001

Cited by 60 publications

(50 citation statements)

References 13 publications

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“…Blood samples for this experiment and for optogenetic stimulation experiments were analyzed for LH content by ELISA also, as reported recently (14). Pulses were detected using the DynPeak algorithm (33).…”

Section: Methodsmentioning

confidence: 98%

Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion

Campos

Herbison

2014

Proc. Natl. Acad. Sci. U.S.A.

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The mechanisms responsible for generating the pulsatile release of gonadotropins from the pituitary gland are unknown. We develop here a methodology in mice for controlling the activity of the gonadotropin-releasing hormone (GnRH) neurons in vivo to establish the minimal parameters of activation required to evoke a pulse of luteinizing hormone (LH) secretion. Injections of Cre-dependent channelrhodopsin (ChR2)-bearing adeno-associated virus into the median eminence of adult GnRH-Cre mice resulted in the selective expression of ChR2 in hypophysiotropic GnRH neurons. Acute brain slice experiments demonstrated that ChR2-expressing GnRH neurons could be driven to fire with high spike fidelity with bluelight stimulation frequencies up to 40 Hz for periods of seconds and up to 10 Hz for minutes. Anesthetized, ovariectomized mice had optical fibers implanted in the vicinity of GnRH neurons within the rostral preoptic area. Optogenetic activation of GnRH neurons for 30-s to 5-min time periods over a range of different frequencies revealed that 10 Hz stimulation for 2 min was the minimum required to generate a pulse-like increment of LH. The same result was found for optical activation of GnRH projections in the median eminence. Increases in LH secretion were compared with endogenous LH pulse parameters measured from ovariectomized mice. Driving GnRH neurons to exhibit simultaneous burst firing was ineffective at altering LH secretion. These observations provide an insight into how GnRH neurons generate pulsatile LH secretion in vivo.GnRH | luteinizing hormone | pulse | optogenetics

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Section: Methodsmentioning

confidence: 98%

Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion

Campos

Herbison

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The intraassay coefficient of variation was 3.66%, and the interassay coefficient of variation was 11.7%. Pulses were confirmed using DynPeak (46).…”

Section: Methodsmentioning

confidence: 99%

Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome

Moore

Prescott

Marshall

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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254

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Polycystic ovarian syndrome (PCOS), the leading cause of female infertility, is associated with an increase in luteinizing hormone (LH) pulse frequency, implicating abnormal steroid hormone feedback to gonadotropin-releasing hormone (GnRH) neurons. This study investigated whether modifications in the synaptically connected neuronal network of GnRH neurons could account for this pathology. The PCOS phenotype was induced in mice following prenatal androgen (PNA) exposure. Serial blood sampling confirmed that PNA elicits increased LH pulse frequency and impaired progesterone negative feedback in adult females, mimicking the neuroendocrine abnormalities of the clinical syndrome. Imaging of GnRH neurons revealed greater dendritic spine density that correlated with increased putative GABAergic but not glutamatergic inputs in PNA mice. Mapping of steroid hormone receptor expression revealed that PNA mice had 59% fewer progesterone receptor-expressing cells in the arcuate nucleus of the hypothalamus (ARN). To address whether increased GABA innervation to GnRH neurons originates in the ARN, a viral-mediated Cre-lox approach was taken to trace the projections of ARN GABA neurons in vivo. Remarkably, projections from ARN GABAergic neurons heavily contacted and even bundled with GnRH neuron dendrites, and the density of fibers apposing GnRH neurons was even greater in PNA mice (56%). Additionally, this ARN GABA population showed significantly less colocalization with progesterone receptor in PNA animals compared with controls. Together, these data describe a robust GABAergic circuit originating in the ARN that is enhanced in a model of PCOS and may underpin the neuroendocrine pathophysiology of the syndrome.GnRH | PCOS | GABA | progesterone receptor | luteinizing hormone G onadotropin-releasing hormone (GnRH) neurons, located in the hypothalamus, control fertility by driving the secretion of the gonadotrophins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from the pituitary gland. The pulse amplitude and frequency of LH and FSH shape the sequence of events that occur at the ovary, including follicular development, gonadal steroid synthesis, and ovulation.

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“…birth-death process) [3] or use pulse detection algorithms [4]. The problem of recovering the model parameters as well as the number, timing, and amplitude of hormone pulses from a limited number of observations is ill-posed (i.e., there could be multiple solutions).…”

Section: Introductionmentioning

confidence: 99%

Deconvolution of Serum Cortisol Levels by Using Compressed Sensing

et al. 2014

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The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropin hormone (ACTH) from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on this problem, a complete satisfactory solution has been elusive. We formulate this question as a non-convex optimization problem, and solve it using a coordinate descent algorithm that has a principled combination of (i) compressed sensing for recovering the amplitude and timing of the secretory events, and (ii) generalized cross validation for choosing the regularization parameter. Using only the observed serum cortisol levels, we model cortisol secretion from the adrenal glands using a second-order linear differential equation with pulsatile inputs that represent cortisol pulses released in response to pulses of ACTH. Using our algorithm and the assumption that the number of pulses is between 15 to 22 pulses over 24 hours, we successfully deconvolve both simulated datasets and actual 24-hr serum cortisol datasets sampled every 10 minutes from 10 healthy women. Assuming a one-minute resolution for the secretory events, we obtain physiologically plausible timings and amplitudes of each cortisol secretory event with R 2 above 0.92. Identification of the amplitude and timing of pulsatile hormone release allows (i) quantifying of normal and abnormal secretion patterns towards the goal of understanding pathological neuroendocrine states, and (ii) potentially designing optimal approaches for treating hormonal disorders.

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DynPeak: An Algorithm for Pulse Detection and Frequency Analysis in Hormonal Time Series

Cited by 60 publications

References 13 publications

Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion

Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion

Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome

Deconvolution of Serum Cortisol Levels by Using Compressed Sensing

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