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.