Ferraris, J. | Search bioRxiv

bioRxiv2026

Stable Network Homeostasis during Multi-Level Postnatal Maturation of the Mouse Tuberoinfundibular Dopamine-Prolactin Axis

The hypothalamus orchestrates endocrine function via specialized neuronal populations that interface with the pituitary gland. While postnatal circuit refinement is a hallmark of most neural systems, its contribution to hypothalamic neuroendocrine networks remains elusive. Among these populations, tuberoin-fundibular dopamine (TIDA) neurons of the arcuate nucleus are the primary source of tonic inhibition of prolactin (Prl), a hormone essential for reproduction, parental physiology, and behavior. While Prl levels surge during early mouse postnatal life, it remains unclear whether the TIDA system is fully developed at birth or undergoes functional maturation. Here, we combined immunofluorescence, slice electrophysiology, and Ca2+ imaging to determine the development of TIDA neurons in mice during the first three postnatal weeks. Expression of dopaminergic markers was sparse at birth but rose substantially after the first week, followed by the onset of median eminence innervation by TIDA axons. Moreover, TIDA firing rate and oscillation frequency progressively increased with age, with action potential properties and rhythmicity maturing in tandem. Strikingly, local network parameters remained stable despite ongoing changes in single-cell properties, as did excitation/inhibition (E/I) balance. These neuronal adaptations paralleled a significant rise in circulating Prl levels. Together, our results delineate a multi-level developmental program within the TIDA system, encompassing molecular, electrophysiological, and endocrine changes. This maturation likely underlies the emergence of functional hypothalamic control over Prl secretion in early life and points to a coordinated controller-effector co-development. Our findings highlight a critical window during which TIDA neuron plasticity may influence long-term neuroendocrine function and reproductive behavior. Significance StatementUnderstanding how neuroendocrine circuits mature is critical for elucidating the developmental origins of hormonal homeostatic control. We reveal that tuberoinfundibular dopamine (TIDA) neurons, which control reproduction by inhibiting the release of the pituitary hormone, prolactin (Prl), undergo a tightly orchestrated postnatal maturation program encompassing population expansion, electrophysiological refinement, and synaptic scaling. Surprisingly, although individual cellular features undergo substantial shifts, network behavior remains remarkably consistent, in parallel with a gradual rise in Prl. This multi-level developmental sequence likely enables the gradual assembly of a functional TIDA-Prl axis. By defining the timeline of TIDA circuit maturation, our work provides a framework for exploring how early-life perturbations may disrupt neuroendocrine development and lead to lifelong alterations in reproductive and parental behaviors.

neuroscience↗

bioRxiv2019

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

AO_SCPCAPBSTRACTC_SCPCAPGiving 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 Ca2+ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro 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, Ih, 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.\n\nSO_SCPLOWIGNIFICANCEC_SCPLOW SO_SCPLOWTATEMENTC_SCPLOWMotherhood 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 - Ih - 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.

neuroscience↗