Biology subjects

Aparicio Arias, J.

Publications and source records attributed to Aparicio Arias, J..

4 recordsLinked to original sources

bioRxiv2026

Population geometry reveals directed coupling and transient bistability in spontaneous pituitary secretion

The pituitary gland operates as an organized signaling network in which endocrine cell populations coordinate hormone secretion, through homotypic and heterotypic interactions, yet the contribution of spontaneous intrinsic activity in shaping population-level dynamics remains poorly understood. Using geometric analysis of population trajectories -- including subspace alignment, manifold separation, and directed coupling metrics -- we identified two classes of spontaneous oscillatory signals associated with distinct cell populations exhibiting asymmetric geometric dominance and a reproducible temporal lag. Our results support that spontaneous activity generates a self-sustained oscillator exhibiting transient bistability, linked to increased physiological demand, with slow oscillations reflecting the properties of an excitatory resonator capable of self-oscillating dynamics without external drive. A low-rank recurrent neural network model recapitulated the empirical geometric landscape under three coupling conditions, confirming that directed population coupling underlies the observed coordination. These findings suggest that intrinsic population dynamics play a central role in coordinating pituitary secretion, with implications for understanding hormonal dysregulation in secretory adenomas and other pituitary disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/716480v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@f5e32borg.highwire.dtl.DTLVardef@1151f9eorg.highwire.dtl.DTLVardef@1cefc2corg.highwire.dtl.DTLVardef@ddac4_HPS_FORMAT_FIGEXP M_FIG C_FIG Structural and functional distinctions between homotypic and heterotypic interactions have been widely described in the pituitary endocrine system. However, whether functional differences in intrinsic calcium time-series dynamics are relevant to pulsatile hormone secretion remains unexplored. Here, we classify the spontaneous activity underlying both homotypic and heterotypic interactions and characterise their synchrony. We find that heterotypic interactions exhibit transient bistability, consistent with a Hopf-type oscillator regime, in which slow oscillations drive secretory output according to physiological demand.

neuroscience↗

bioRxiv2025

Non-Invasive Photoacoustic Imaging of Cerebral Oxygenation and Hemoglobin Content in Awake Mice

IntroductionInvestigating cerebral oxygen saturation dynamics in awake animal models remains technically challenging due to motion artifacts and anesthesia-related biases. Here, we introduce a novel high-resolution ultrasound-photoacoustic (PA) imaging approach enabling real-time, non-invasive monitoring of deep cerebrovascular oxygenation dynamics in awake mice with intact skulls. Materials and MethodsSwiss male and female mice (n = 5-6) were head-fixed using a customized holder adapted to the Neurotar Mobile HomeCage floating platform. High-resolution ultrasound combined with PA imaging (VevoLAZR-X, VisualSonics) was used to discriminate oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in multiple brain regions. Cerebrovascular responses were assessed under three paradigms: (i) baseline awake state vs. 2% isoflurane anesthesia, and (ii) right whisker stimulation to probe sensory-driven hemodynamics. ResultsPA imaging successfully resolved deep-brain oxygenation in awake, intact-skull mice. Under isoflurane anesthesia, we observed a rapid and transient increase in cerebrovascular sO{square} (p < 0.01). During whisker stimulation, we detected robust, region-specific increases in total hemoglobin, reflecting localized neurovascular coupling in awake mice. ConclusionsThis study establishes high-resolution PA imaging as a powerful, non-invasive tool to monitor cerebrovascular oxygenation dynamics in awake mice. By integrating baseline, anesthetic, and sensory paradigms, we demonstrate its potential to dissect neurovascular physiology without the confounding effects of anesthesia. These findings provide new opportunities for preclinical neuroscience research and translational applications investigating cerebral oxygen metabolism.

neuroscience↗

bioRxiv2025

Daily intermittent fasting is an effective multiscale treatment in preclinical models of absence epilepsy

Absence epilepsy (AE) is characterized by brief but frequent seizures with loss of consciousness. Existing treatments have heavy side effects, are only partially effective and do not address the comorbidities, including cognitive and social deficits. A tripartite link between seizures, cognitive deficits and diet has been established. We focused on intermittent fasting (IF), a regime where daily periods of fasting alternate with periods of food intake, with no restrictions in the type or quantity of food consumed. To date, the effects of IF on infantile epilepsy have not been addressed. We evaluated the therapeutic potential of a daily, one-month protocol of IF on three established mouse models of AE: the Grm7AAA KI mouse, the Scn2a haploinsufficiency mouse and the pharmacologically-induced AY-9944 mouse model. We show a reduction of the seizure frequency in all models, as well as an improvement of the sociability deficits observed in two of the models, with no adverse effects. Focusing on the Grm7AAA KI model, we performed RNA sequencing in a one of the key brain areas of the absence seizure circuit, the thalamus. We detected a deregulation of genes involved in vascularization associated with the development of malformed blood vessels in epileptic mice. Along with its anti-seizure effects, IF was able to counteract both abnormal gene expression and vessel morphology. This study demonstrates for the first time the positive effects of IF on AE and could facilitate the implementation of the diet in clinical trials.

neuroscience↗

bioRxiv2022

Differential reduction of neuropathic pain symptoms by mGlu4-mediated neuromodulation of amygdala circuits

Neuropathic pain is a common health problem, resulting in exacerbated response to noxious and non noxious stimuli, as well as impaired emotional and cognitive responses. Unfortunately, neuropathic pain is also one of the most difficult pain syndromes to manage, highlighting the importance of better understanding of the brain regions and neuromodulatory mechanisms involved in its regulation. Among the many interconnected brain areas which process pain, the amygdala is known to play an important role in the integration of sensory and emotional pain signals. Here, we questioned the ability of a recently identified neuromodulatory mechanisms associated to the metabotropic glutamate receptors mGlu4 in the amygdala to modulate neuropathic pain. In a murine model of peripheral mononeuropathy induced by a chronic constriction of the sciatic nerve, we demonstrate that pharmacological activation of amygdala mGlu4 receptors efficiently alleviates sensory and depressive-like symptoms in both male and female mice. Moreover, we reveal a differential modulation of those symptoms, activating mGlu4 receptors in the controlateral amygdala, relatively to the side of the mononeuropathy, is necessary and sufficient to relieve both sensory and depressive-like symptoms while ipsilateral activation solely reduces depressive-like symptoms. Furthermore, using photopharmacology, a recent strategy allowing a precise spatiotemporal photocontrol of deep brain endogenous targets, we further demonstrate the rapid and reversible action of mGlu4-mediated neuromodulation on neuropathic pain symptoms. Finally, coupling photopharmacology and analgesic conditioned place preference, we show an important pain-reducing effect of mGlu4 activation. Taken together, these data highlight the analgesic potential of enhancing amygdala mGlu4 activity to counteract neuropathy in the hope of improving existing treatments.

neuroscience↗