Long-term Recordings of Arcuate Nucleus Kisspeptin Neurons Across the Mouse Estrous Cycle

Szilvia Vas, Ellen Wall, Ziyue Zhou, Lajos Kalmar, Su Young Han, Allan E Herbison
Endocrinology, Volume 165, Issue 3, March 2024, bqae009
https://doi.org/10.1210/endocr/bqae009

Abstract

The arcuate nucleus kisspeptin (ARN^KISS) neurons represent the GnRH pulse generator that likely drives pulsatile gonadotropin secretion in all mammals. Using an improved GCaMP fiber photometry system enabling long-term continuous recordings, we aimed to establish a definitive profile of ARN^KISS neuronal activity across the murine estrous cycle. As noted previously, a substantial reduction in the frequency of ARN^KISS neuron synchronization events (SEs) occurs on late proestrus and extends into estrus. The SE amplitude remains constant throughout the cycle. During metestrus, we unexpectedly detected many multipeak SEs where many SEs occurred rapidly, within 160 seconds of each other. By applying a machine learning-based, k-means clustering analysis, we were further able to detect substantial within-stage variability in the patterns of pulse generator activity. Estrous cycle-dependent changes in SE activity occurred around the time of lights on and off. We also find that a mild stressor such as vaginal lavage reduces ARN^KISS neuron SE frequency for up to 3 hours. These observations provide a comprehensive account of ARN^KISS neuron activity across the estrous cycle, highlight a new pattern of multipeak SE activity, and introduce a new k-means clustering approach for analyzing ARN^KISS neuron population behavior.

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