The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice.

Unipolar brush cells (UBCs) are excitatory interneurons in the cerebellar cortex that receive mossy fiber (MF) inputs and excite granule cells. The UBC population responds to brief burst activation of MFs with a continuum of temporal transformations, but it is not known how UBCs transform the diverse range of MF input patterns that occur in vivo. Here, we use cell-attached recordings from UBCs in acute cerebellar slices to examine responses to MF firing patterns that are based on in vivo recordings. We find that MFs evoke a continuum of responses in the UBC population, mediated by three different types of glutamate receptors that each convey a specialized component. AMPARs transmit timing information for single stimuli at up to 5 spikes/s, and for very brief bursts. A combination of mGluR2/3s (inhibitory) and mGluR1s (excitatory) mediates a continuum of delayed, and broadened responses to longer bursts, and to sustained high frequency activation. Variability in the mGluR2/3 component controls the time course of the onset of firing, and variability in the mGluR1 component controls the duration of prolonged firing. We conclude that the combination of glutamate receptor types allows each UBC to simultaneously convey different aspects of MF firing. These findings establish that UBCs are highly flexible circuit elements that provide diverse temporal transformations that are well suited to contribute to specialized processing in different regions of the cerebellar cortex.