Multi-dimensional oscillatory activity of mouse GnRH neurons in vivo

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.

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.