Multi-dimensional oscillatory activity of mouse GnRH neurons in vivo
Curation statements for this article:-
Curated by eLife
eLife assessment:
This valuable study investigates the oscillatory activity of gonadotropin-releasing hormone (GnRH) neurones in mice using GCaMP fiber photometry. It demonstrates three distinct patterns of oscillatory activity that occur in GnRH neurons comprising low-level rapid baseline activity, abrupt short-duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and prolonged oscillating increase in activity responsible for the relatively short-lived preovulatory LH surge. The evidence presented in the study is solid, offering theoretical implications for understanding the behaviour of GnRH neurones in the context of reproductive physiology, and will be of interest to researchers in neuroendocrinology and reproductive biology.
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Abstract
The gonadotropin-releasing hormone (GnRH) neurons represent the key output cells of the neural network controlling mammalian fertility. We used GCaMP fiber photometry to record the population activity of the GnRH neuron distal projections in the ventral arcuate nucleus where they merge before entering the median eminence to release GnRH into the portal vasculature. Recordings in freely behaving intact male and female mice revealed abrupt 5-min duration increases in activity that correlated perfectly with the appearance of a subsequent pulse of luteinizing hormone (LH). In addition, GnRH neuron dendrons exhibited a low level of clustered, rapidly fluctuating baseline activity in both sexes that did not change through the estrous cycle. In female mice, a gradual increase in basal activity that exhibited ∼80-min oscillations began in the afternoon of proestrus and lasted for 12 h. This was associated with the onset of the LH surge that ended several hours before the fall in GCaMP signal. Abrupt episodes of GCaMP activity continued to occur on top of the rising surge baseline before ceasing in estrus. These observations provide the first description of GnRH neuron activity in freely behaving animals. They demonstrate three distinct patterns of oscillatory activity occur in GnRH neurons. These are comprised of low-level rapid baseline activity, abrupt short-duration oscillations that drive pulsatile gonadotropin secretion and, in females, a gradual and prolonged oscillating increase in activity responsible for the relatively short-lived preovulatory LH surge.
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eLife assessment:
This valuable study investigates the oscillatory activity of gonadotropin-releasing hormone (GnRH) neurones in mice using GCaMP fiber photometry. It demonstrates three distinct patterns of oscillatory activity that occur in GnRH neurons comprising low-level rapid baseline activity, abrupt short-duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and prolonged oscillating increase in activity responsible for the relatively short-lived preovulatory LH surge. The evidence presented in the study is solid, offering theoretical implications for understanding the behaviour of GnRH neurones in the context of reproductive physiology, and will be of interest to researchers in neuroendocrinology and reproductive biology.
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Reviewer #1 (Public Review):
Summary:
The authors aimed to investigate the oscillatory activity of GnRH neurones in freely behaving mice. By utilising GCaMP fiber photometry, they sought to record real-time neuronal activity to understand the patterns and dynamics of GnRH neuron firing and their implications for reproductive physiology.
Strengths:
(1) The use of GCaMP fiber photometry allows for high temporal resolution recordings of neuronal activity, providing real-time data on the dynamics of GnRH neurones.
(2) Recording in freely behaving animals ensures that the findings are physiologically relevant and not artifacts of a controlled laboratory environment.
(3) The authors used statistical methods to characterise the oscillatory patterns, ensuring the reliability of their findings.
Weaknesses:
(1) While the study identifies distinct …
Reviewer #1 (Public Review):
Summary:
The authors aimed to investigate the oscillatory activity of GnRH neurones in freely behaving mice. By utilising GCaMP fiber photometry, they sought to record real-time neuronal activity to understand the patterns and dynamics of GnRH neuron firing and their implications for reproductive physiology.
Strengths:
(1) The use of GCaMP fiber photometry allows for high temporal resolution recordings of neuronal activity, providing real-time data on the dynamics of GnRH neurones.
(2) Recording in freely behaving animals ensures that the findings are physiologically relevant and not artifacts of a controlled laboratory environment.
(3) The authors used statistical methods to characterise the oscillatory patterns, ensuring the reliability of their findings.
Weaknesses:
(1) While the study identifies distinct oscillatory patterns in GnRH neurones' calcium dynamics, it falls short in exploring the functional implications of these patterns for GnRH pulsatility and overall reproductive physiology.
(2) The study lacks a broader discussion to include comparisons with existing studies on GnRH neurone activity and pulsatility and highlight how the findings of this study align with or differ from previous research and what novel contributions are made.
(3) The authors aimed to characterise the oscillatory activity of GnRH neurons and successfully identified distinct oscillatory patterns. The results support the conclusion that GnRH neurons exhibit complex oscillatory behaviours, which are critical for understanding their role in reproductive physiology. However, it has not been made clear what exactly the authors mean by "multi-dimensional oscillatory patterns" and how has this been shown.
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Reviewer #2 (Public Review):
Summary:
In this manuscript, the authors report GCaMP fiber-photometry recordings from the GnRH neuron distal projections in the ventral arcuate nucleus. The recordings are taken from intact, male and female, freely behaving mice. The report three patterns of neuronal activity:
(1) Abrupt increases in the Ca2+ signals that are perfectly correlated with LH pulses.
(2) A gradual, yet fluctuating (with a slow ultradian frequency), increase in activity, which is associated with the onset of the LH surge in female animals.
(3) Clustered (high frequency) baseline activity in both female and male animals.
Strengths:
The GCaMP fiber-photometry recordings reported here are the first direct recordings from GnRH neurones in vivo. These recordings have uncovered a rich repertoire of activity suggesting the integration …
Reviewer #2 (Public Review):
Summary:
In this manuscript, the authors report GCaMP fiber-photometry recordings from the GnRH neuron distal projections in the ventral arcuate nucleus. The recordings are taken from intact, male and female, freely behaving mice. The report three patterns of neuronal activity:
(1) Abrupt increases in the Ca2+ signals that are perfectly correlated with LH pulses.
(2) A gradual, yet fluctuating (with a slow ultradian frequency), increase in activity, which is associated with the onset of the LH surge in female animals.
(3) Clustered (high frequency) baseline activity in both female and male animals.
Strengths:
The GCaMP fiber-photometry recordings reported here are the first direct recordings from GnRH neurones in vivo. These recordings have uncovered a rich repertoire of activity suggesting the integration of distinct "surge" and "pulse" generation signals, and an ultradian rhythm during the onset of the surge.
Weaknesses:
The data analysis method used for the characterisation of the ultradian rhythm observed during the onset of the surge is not detailed enough. Hence, I'm left wondering whether this rhythm is in any way correlated with the clusters of activity observed during the rest of the cycle and which have similar duration.
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