Biology subjects

Tabak, J.

Publications and source records attributed to Tabak, J..

5 recordsLinked to original sources

bioRxiv2026

Differential control of corticotroph Ca2+ signalling by corticotrophin-releasing hormone and arginine vasopressin

Corticotroph cells convert hypothalamic inputs into adrenocorticotrophic hormone secretion via intracellular calcium (Ca2+) signalling, but how they integrate corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) across physiological concentration ranges remains unclear. Here, we quantified intracellular Ca2+ responses in isolated rat corticotrophs to CRH and AVP, applied alone and in combination, to characterise response magnitude, temporal dynamics, and cell recruitment. Both secretagogues increased Ca2+ signalling in a concentration-dependent manner, but with distinct effects: AVP generally evoked larger responses, faster response onset, and greater cell recruitment than CRH when applied alone. Under co-stimulation, increasing CRH concentration increased the proportion of cells classified as synergistic without altering positive synergy values, suggesting CRH-dependent control of interaction likelihood rather than interaction strength. Marked cell-to-cell heterogeneity was observed across all conditions, consistent with corticotroph subpopulations differing in activation thresholds. Together, these findings show that AVP drives broad corticotroph recruitment, whereas CRH modulates how corticotrophs integrate convergent inputs, defining complementary roles in shaping pituitary output.

neuroscience↗

bioRxiv2025

Beyond Locomotion: How Specialized Motor Rhythms Enable Vertebrate Escape from Capture

Escape behaviors following capture are crucial for survival, yet their underlying neurobiological mechanisms remain poorly understood. We investigated how Xenopus laevis tadpoles use struggling movements to escape head restraint. High-speed video tracking revealed a stereotyped sequence of body flexions with distinct kinematics during capture and release. We further recorded motoneuron and motor nerve activity along the body axis during fictive struggling to reconstruct biologically realistic struggling commands, to drive the movement of a biomechanically detailed tadpole model. Simulations showed that struggling - characterized by long-duration, low-frequency, caudorostral muscle activation - was optimized to generate escape forces. Notably, hydrodynamic thrust alone proved insufficient for release. However, direct mechanical interactions between the tadpoles body and the restraining object generated additional reactive forces that facilitated escape. These findings demonstrate how animals use coordinated motor outputs and body mechanics to interact with environment to generate maximal freeing forces as the fundamental escape strategy.

neuroscience↗

bioRxiv2024

Population Bursts in a Modular Neural Network as a Mechanism for Synchronized Activity in KNDy Neurons

The pulsatile activity of gonadotropin-releasing hormone neurons (GnRH neurons) is a key factor in the regulation of reproductive hormones. This pulsatility is orchestrated by a network of neurons that release the neurotransmitters kisspeptin, neurokinin B, and dynorphin (KNDy neurons), and produce episodic bursts of activity driving the GnRH neurons. We show in this computational study that the features of coordinated KNDy neuron activity can be explained by a neural network in which connectivity among neurons is modular. That is, a network structure consisting of clusters of highly-connected neurons with sparse coupling among the clusters. This modular structure, with distinct parameters for intracluster and intercluster coupling, also yields predictions for the differential effects of the co-released transmitters neurokinin B and dynorphin. In particular, it provides one possible explanation for how the excitatory neurotransmitter neurokinin B and the inhibitory neurotransmitter dynorphin can both increase the degree of synchronization among KNDy neurons. Author summarySince the discovery of a small population of hypothalamic neurons that secrete kisspeptin, neurokinin B, and dynorphin (KNDy neurons), there has been interest in their role as a pacemaker for the pulsatile release of key reproductive hormones. A fundamental question is what mechanism coordinates KNDy neuron activity to generate population bursts. Optical imaging of the KNDy network at single-neuron resolution has revealed that individual KNDy neurons participate in many, but not all, population bursts. It has also shown that the order in which the neurons are recruited in each burst could be highly determined in some animals but not in others. We demonstrate here that these observations can be explained by a neural network with a modular structure. We also show how such a structure can explain the paradoxical finding that both the excitatory neurotransmitter neurokinin B and the inhibitory neurotransmitter dynorphin can act to increase the degree of synchronization among the KNDy neurons.

neuroscience↗

bioRxiv2021

The sodium leak channel NALCN encodes the major background sodium ion conductance in murine anterior pituitary cells

The pituitary gland produces and secretes a variety of hormones that are essential to life, such as for the regulation of growth and development, metabolism, reproduction, and the stress response. This is achieved through an intricate signalling interplay between the brain and peripheral feedback signals that shapes pituitary cell excitability by regulating ion channel properties of these cells. In addition, endocrine anterior pituitary cells fire action potentials spontaneously to regulate intracellular calcium ([Ca2+]i) level, an essential signalling conduit for hormonal secretion. To this end, pituitary cells have to critically regulate their resting membrane potential (RMP) close to firing threshold, but the molecular identity of the ionic mechanisms involved remains largely unknown. Here, we revealed that the sodium leak channel NALCN, known to modulate neuronal excitability elsewhere in the brain, acts to regulate excitability in the mouse anterior endocrine pituitary cells. Using viral transduction combined with powerful electrophysiology methods and calcium imaging, we show that NALCN forms the major Na+ leak conductance in these cells, appropriately tuning cellular RMP for sustaining spontaneous firing activity. Genetic interruption of NALCN channel activity drastically hyperpolarised the cells, suppressing firing and ([Ca2+]i) oscillations. Remarkably, we uncover that NALCN conductance formed a very small fraction of the total cell conductance, but yet had a profound impact on pituitary cell excitability. Our results also provide a possible mechanism through which hypothalamic and hormone feedback signals can powerfully affect pituitary activity to influence hormonal function.

physiology↗

bioRxiv2020

Dynamic hormone control of stress and fertility

Neuroendocrine axes display a remarkable diversity of dynamic signalling processes relaying information between the brain, endocrine glands, and peripheral target tissues. These dynamic processes include oscillations, elastic responses to perturbations, and plastic long term changes observed from the cellular to the systems level. While small transient dynamic changes can be considered physiological, larger and longer disruptions are common in pathological scenarios involving more than one neuroendocrine axes, suggesting that a robust control of hormone dynamics would require the coordination of multiple neuroendocrine clocks. The idea of apparently different axes being in fact exquisitely intertwined through neuroendocrine signals can be investigated in the regulation of stress and fertility. The stress response and the reproductive cycle are controlled by the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Hypothalamic-Pituitary-Gonadal (HPG) axis, respectively. Despite the evidence surrounding the effects of stress on fertility, as well as of the reproductive cycle on stress hormone dynamics, there is a limited understanding on how perturbations in one neuroendocrine axis propagate to the other. We hypothesize that the links between stress and fertility can be better understood by considering the HPA and HPG axes as coupled systems. In this manuscript, we investigate neuroendocrine rhythms associated to the stress response and reproduction by mathematically modelling the HPA and HPG axes as a network of interlocked oscillators. We postulate a network architecture based on physiological data and use the model to predict responses to stress perturbations under different hormonal contexts: normal physiological, gonadectomy, hormone replacement with estradiol or corticosterone (CORT), and high excess CORT (hiCORT) similar to hypercortisolism in humans. We validate our model predictions against experiments in rodents, and show how the dynamic responses of these endocrine axes are consistent with our postulated network architecture. Importantly, our model also predicts the conditions that ensure robustness of fertility to stress perturbations, and how chronodisruptions in glucocorticoid hormones can affect the reproductive axis ability to withstand stress. This insight is key to understand how chronodisruption leads to disease, and to design interventions to restore normal rhythmicity and health.

systems biology↗