Adaptive resetting of tuberoinfundibular dopamine (TIDA) network activity during lactation in mice

Abstract

<jats:title>A<jats:sc>BSTRACT</jats:sc></jats:title><jats:p>Giving birth triggers a wide repertoire of physiological and behavioural changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the central nervous system, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca<jats:sup>2+</jats:sup> imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons <jats:italic>in vitro</jats:italic> to examine if they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stable. An increase in the hyperpolarization-activated mixed cation current, I<jats:sub>h</jats:sub>, possibly through unmasking as dopamine release drops during nursing, may explain the reconfiguration of TIDA rhythms. These findings identify a reversible plasticity in hypothalamic network activity that can serve to adapt the dam for motherhood.</jats:p><jats:sec><jats:title>S<jats:sc>ignificance</jats:sc> S<jats:sc>tatement</jats:sc></jats:title><jats:p>Motherhood requires profound behavioural and physiological adaptations to enable caring for offspring, but the underlying CNS changes are poorly understood. Here, we show that during lactation, neuroendocrine dopamine neurons, the “TIDA” cells that control prolactin secretion, reorganize their trademark oscillations to discharge in faster frequencies. Unlike previous studies, which typically have focused on structural and transcriptional changes during pregnancy and lactation, we demonstrate a functional switch in activity and one that, distinct from previously described puerperal modifications, reverses fully upon weaning. We further provide evidence that a specific conductance – I<jats:sub>h</jats:sub> - may underlie the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity.</jats:p></jats:sec>

Current Insights in Prolactin Signaling and Ovulatory Function

“…Therefore, increased PRL secretion under both physiological and pathological conditions mostly results from the removal of dopamine-inhibiting pathways. Hence, most prolactin-releasing factors (PRFs) act indirectly through the deactivation of the TIDA system, although direct effects on lactotrophs and other mechanisms of action (which have not been completely clarified) are certainly present [270][271][272]. Although PRL is well known to stimulate hypothalamic dopamine secretion, thereby exerting negative feedback regulation on its own release, autocrine or paracrine actions of PRL on lactotroph cells have also been suggested [273].…”

“…The tonic release of dopamine (DA) from these neuronal endings provides an appropriate level of inhibition of PRL release from lactotrophs (LTH) under physiological conditions [8]. PRLR expression in TIDA neurons is crucial for the operation of such a short negative feedback loop in the DA/PRL system [270][271][272]. PRL in a sufficiently high concentration causes suppression of GnRH neurons that are scattered between the preoptic area (POA; marked with a dashed red line) and ARC in the shape of an "inverted Y" [82].…”