Biology subjects

Broberger, C.

Publications and source records attributed to Broberger, C..

6 recordsLinked to original sources

bioRxiv2026

Cellular and Network Effects of Introducing Connexin-36 Expression in an Uncoupled Neuronal Population in the Mouse Hypothalamus

Electrical synapses are prevalent throughout nervous systems, including the mammalian brain. Several lines of evidence implicate these gap junction connections in several important roles in neural networks. Yet, progress has been hampered by a shortage of experimental tools to investigate their function with sufficient precision. In an effort to address this deficit, we here take advantage of a curious species-difference in electrical coupling in tuberoinfundibular dopamine (TIDA) neurons of the rodent hypothalamus. In rats, these cells exhibit strong electrical coupling, generating stereotyped, slow oscillations that are synchronized across the population. In contrast, mouse TIDA neurons lack gap junctions and display diverse, faster, and asynchronous oscillations. Motivated by this natural discrepancy, we designed a gain-of-function strategy to induce localized and robust expression of the main pore-forming protein of neuronal gap junctions, connexin-36 (Cx36), in mouse TIDA neurons by viral vectors. This perturbation yielded electrical coupling that was weaker than the rat TIDA system, but on par with many other brain populations connected by gap junctions. Cx36 overexpression resulted in significantly increased auto- and cross-correlation, as well as augmented functional connectivity, in agreement with the induction of electrical synapses in the population. Yet, these measures were modest in comparison with rat TIDA neurons, and Cx36 overexpression failed to alter serum levels of the hormone prolactin, which is controlled by this neuroendocrine system. These findings highlight the potential and limitations of experimentally inducing electrical synapses in a natively uncoupled system, and suggest directions for future improvements.

neuroscience↗

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↗

bioRxiv2026

Cortical Layer 6b Persistent Subplate Neurons Reciprocally Connect Sensorimotor Areas and Inversely Reflect Somatosensory Engagement

Persistent subplate neurons in layer 6b (L6b) of the cerebral cortex have long been assumed to be a passive remnant of early development. Recent findings are challenging this concept, but the functional role of L6b remains mysterious. A large group of L6b neurons express Connective Tissue Growth Factor (Ctgf). Here, we mapped L6bCtgf neurons throughout the cortex and found the highest density in primary sensorimotor areas. Cortical L6bCtgf projections are ipsilaterally restricted and origin-site specific, with notable reciprocity, whereas innervation of the thalamus is modality-matched. L6bCtgf neurons are electrically diverse and form excitatory synapses with both pyramidal cells and interneurons. In freely moving mice, these neurons are highly active and have prominent task-specific and temporally locked responses to external stimuli. These responses are dominated by paradoxical population silencing with escalating task engagement. Thus, L6bCtgf neurons may keep cortical ensembles in a state of alertness and available to process cognate stimuli. HIGHLIGHTSO_LIL6bCtgf neurons form origin-and layer-specific ipsilateral cortical connections. C_LIO_LIElectrically heterogeneous L6bCtgf neurons excite multiple classes of cortical neurons. C_LIO_LIBarrel cortex L6bCtgf neurons are highly active in freely moving mice. C_LIO_LISomatosensory exploration paradoxically silences active barrel cortex L6bCtgf neurons. C_LI

neuroscience↗

bioRxiv2025

Nutritionally responsive PMv DAT neurons are dynamically regulated during pubertal transition

Pubertal development is tightly regulated by energy balance. The crosstalk between metabolism and reproduction is orchestrated by complex neural networks and leptin action in the hypothalamus plays a critical role. The ventral premammillary nucleus (PMv) leptin receptor (LepRb) neurons act as an essential relay for leptin action on reproduction. Here, we show that mouse PMv cells expressing the dopamine transporter (DAT) gene, Slc6a3 (PMvDAT) form a novel subpopulation of LepRb neurons. Virtually all PMvDAT neurons expressed Lepr mRNA and responded to acute leptin treatment. Electrophysiological recordings from DATCRE;tdTomato mice showed that PMvDAT cells in prepubertal females have a hyperpolarized resting membrane potential compared to diestrous females. Slc6a3 mRNA expression in the PMv was higher in prepubertal than in adult females. In prepubertal females Slc6a3 mRNA expression was higher in overnourished females from small size litters than in controls. Prepubertal Lepob females showed decreased PMv Slc6a3 mRNA expression, that recovered to control levels after 3 days of leptin injections. Using a tracer adenoassociated virus in the PMv of adult DATCre;Kiss1hrGFP females, we observed PMvDAT projections in the anteroventral periventricular and periventricular nucleus (AVPV/PeN), surrounding Kiss1hrGFP neurons, a population critical for sexual maturation and positive estrogen feedback in females. The DATCRE;tdTomato projections to the AVPV were denser in adult than in prepubertal females. In adults, they surrounded tyrosine hydroxylase neurons. Overall, these findings suggest that the DAT expressing PMvLepRb subpopulation play a role in leptin regulation of sexual maturation via actions on AVPV kisspeptin/tyrosine hydroxylase neurons. Significance StatementWomen with excess or low energy stores (e.g., obesity or anorexia) have reproductive deficits, including altered puberty onset, disruption of reproductive cycles and decreased fertility. If able to conceive, they show higher risks of miscarriages and preterm birth. The hypothalamic circuitry controlling the interplay between metabolism and reproduction is poorly defined. Neurons in the ventral premammillary nucleus express the leptin receptor and play a key role in the metabolic control of reproduction. Those neurons are functionally and phenotypically heterogeneous. Here we show that a subset of leptin-sensitive neurons co-expresses the dopamine transporter (DAT), is dynamically regulated during pubertal transition and with nutrition and projects to brain sites relevant for sexual maturation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/636271v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@cb8223org.highwire.dtl.DTLVardef@ccf560org.highwire.dtl.DTLVardef@17e58org.highwire.dtl.DTLVardef@de021_HPS_FORMAT_FIGEXP M_FIG C_FIG The ventral premammillary nucleus of the hypothalamus plays an essential role in the metabolic control of reproduction. Puberty brings large changes to a subpopulation of PMvLepRb cells expressing the dopamine transporter (PMvDAT). DAT gene expression is higher in prepubertal than in adults and is regulated by leptin in prepubertal females. Dynamic projections from PMvDAT cells contact the kisspeptin and tyrosine hydroxylase (TH) populations in the AVPV/PeN during puberty, a critical time for the appearance of these cells in the AVPV/PeN.

neuroscience↗

bioRxiv2023

Maternal hormones engage a dormant monomorphic aggression circuit, leading to the introduction of an innate behavior in adulthood in females

Aggression, a sexually dimorphic behaviour, is prevalent in males and typically absent in virgin females. Following parturition, however, the transient expression of aggression in adult female mice protects pups from predators and infanticide by male conspecifics. While maternal hormones are known to elicit nursing, their potential role in maternal aggression remains elusive. Here, we show in mice that a molecularly defined subset of ventral premammillary (PMvDAT) neurons, instrumental for intermale aggression, switch from quiescence to a hyperexcitable state during lactation. We identify that the maternal hormones prolactin and oxytocin excite these cells through actions that include T-type Ca2+ channels. Optogenetic manipulation or genetic ablation of PMvDAT neurons profoundly affects maternal aggression, while activation of these neurons impairs the expression of non-aggression-related maternal behaviours. This work identifies a monomorphic neural substrate that can incorporate hormonal cues to enable the transient expression of a dormant behavioural program in lactating females.

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↗