Multi-dimensional oscillatory activity of mouse GnRH neurons in vivo

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.