Biology subjects

Matarazzo, V.

Publications and source records attributed to Matarazzo, V..

4 recordsLinked to original sources

bioRxiv2025

Early emergence for thermal processing in the neonatal somatosensory cortex and its perturbation in ASD

Thermal perception is essential for neonatal adaptation and survival, yet the cortical processing during early development remains unknown. Here we show that non-painful cool, but not warm, orofacial stimulation evokes robust and lateralized activation in the whisker-related somatosensory cortex (wS1) of neonatal mice during the first postnatal week. These responses, revealed by mesoscopic in vivo imaging and electrophysiological recordings, partly overlap with tactile representations from the same region, indicating early regionalization of thermotactile maps. In a mouse model of autism spectrum disorder deficient for Magel2, we found altered spatial encoding of cool stimuli accompanied by increased local field potential activity, suggestive of cortical hyperexcitability. Our findings establish that the cortical processing of cool sensory information emerges from the first week of life and is disrupted in a genetic model of autism, highlighting early vulnerability of thermosensory circuits and their potential contributions to neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

The oxytocin-modulated brain circuit that synchronizes heart rate with breathing

The variation in heart rate in phase with breathing, called respiratory sinus arrhythmia (RSA), is cardio-protective1,2. RSA amplitude provides an index of health and physical fitness used both clinically, and by the broader population using "smart" watches. Relaxation and positive socio-emotional states can amplify RSA3, yet the underlying mechanism remains largely unknown. Here, we identify a hypothalamus-brainstem neuronal network through which the neuromodulator oxytocin (OT), known for its relaxing and prosocial effects4, amplifies RSA during calming behavior. OT neurons from the caudal paraventricular nucleus in the hypothalamus were found to regulate the activity of a subgroup of inhibitory neurons in the pre-Botzinger complex, the brainstem neuronal group that generates the inspiratory rhythm. Specifically, OT amplifies the inspiratory glycinergic input from pre-Botzinger complex neurons to cardiac-innervating parasympathetic neurons in the nucleus ambiguus. This leads to amplified respiratory modulation of parasympathetic activity to the heart, thereby amplifying RSA. Behaviorally, OT neurons participate in the restoration of RSA amplitude during recovery from stress. This work shows how a central action of OT induces a physiologically beneficial regulation of cardiac activity during a calming behavior, providing a foundation for therapeutic strategies for anxiety disorders and coping with stress. Furthermore, it identifies a phenotypic signature of a subpopulation of neurons controlling RSA, namely pre-Botzinger complex neurons expressing the OT-receptor, enabling the specific modulation of RSA amplitude to resolve its physiological and psychological functions.

neuroscience↗

bioRxiv2020

Acute neonatal oxytocin impacts hippocampal network development and restores adult social memory deficits in a mouse model of autism spectrum disorder.

Oxytocin is a master regulator of the social brain. In some animal models of autism, notably in Magel2 tm1.1Mus-deficient mice, peripheral administration of oxytocin in infancy improves social behaviors until adulthood. However, neither the mechanisms responsible for social deficits nor the mechanisms by which such oxytocin administration has long-term effects are known. Here, we aimed to clarify these oxytocin-dependent mechanisms focusing on social memory performance. We showed that Magel2tm1.1Mus-deficient mice present a deficit in social memory and studied the hippocampal circuits underlying this memory. We showed a co-expression of Magel2 and oxytocin-receptor in the dentate gyrus and CA2/CA3 hippocampal regions. Then, we demonstrated: an increase of the GABAergic activity of CA3-pyramidal cells associated with an increase in the quantity of oxytocin-receptors and of somatostatin interneurons. We also revealed a delay in the GABAergic development sequence in Magel2tm1.1Mus-deficient pups, linked to phosphorylation modifications of KCC2. Above all, we demonstrated the positive effects of subcutaneous administration of oxytocin in the mutant neonates, restoring neuronal alterations and social memory. Although clinical trials are debated, this study highlights the mechanisms by which peripheral oxytocin-administration in neonates impacts the brain and demonstrates the therapeutic value of oxytocin to treat infants with autism spectrum disorders.

neuroscience↗

bioRxiv2019

Characterization and rescue by oxytocin of an atypical thermo-sensory reactivity in neonatal mice lacking the autism-associated gene Magel2.

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we identified that neonatal mice lacking the autism-associated gene Magel2 fail to react to cool sensory stimuli, while autonomic thermoregulatory function is active. This neonatal deficit was mimicked in control neonates by chemogenetic inactivation of oxytocin neurons. Importantly, intranasal administration of oxytocin was able to rescue the phenotype and brain Erk signaling impairment in mutants. This preclinical study establishes for the first-time early life impairments in thermosensory integration and shows the therapeutic potential benefits of intranasal oxytocin treatment on neonatal atypical sensory reactivity.

neuroscience↗