Biology subjects

Fossat, P.

Publications and source records attributed to Fossat, P..

5 recordsLinked to original sources

bioRxiv2026

Superficial spinal Tac1-lineage neurons are polymodal nociceptive

Tac1-lineage neurons in the spinal dorsal horn have been implicated in coping behavior in response to sustained noxious stimuli, but their developmental origin, cellular heterogeneity, and functional contribution remain incompletely understood. Here, we characterized the molecular identity, developmental trajectory, electrophysiological properties, and sensory responses of spinal Tac1-lineage neurons. In adults, Tac1-lineage neurons comprised a heterogeneous population of excitatory and inhibitory interneurons and excitatory projection neurons distributed across the superficial dorsal horn. In contrast, at embryonic day 16.5, Tac1-lineage neurons in laminae I/IIo were exclusively projection neurons, revealing a marked developmental transition in the composition of the Tac1 lineage. Electrophysiological recordings from spinal cord slices further demonstrated substantial functional heterogeneity, with most Tac1-lineage neurons exhibiting phasic or single-spike firing and smaller populations displaying tonic or reluctant firing. In vivo calcium imaging in anesthetized mice revealed prominent responses to noxious mechanical and thermal stimulation. Interestingly, Tac1-lineage neurons used distinct strategies to encode cold and heat intensity. Together, these findings reveal pronounced developmental and functional heterogeneity within the Tac1 lineage and demonstrate that adult Tac1-lineage neurons are predominately polymodal nociceptive.

neuroscience↗

bioRxiv2026

Spinotrode: long-term intraspinal electrophysiological recordings to unravel dorsal horn neuron dynamics in behaving mice

Recording single-unit neural activity in the spinal cord in freely moving rodents is crucial for understanding spinal network dynamics but remains challenging due to specific biomechanical constraints. So far, the vast majority of studies have been conducted in anesthetized or restrained animals, limiting the correlation of neuronal activity with naturalistic behaviours. Here we introduce the Spinotrode, a vertebral implant able to stably record signals (over several weeks) at the single-cell level in the bilateral dorsal horns of adult mice. It is engineered to minimize postural constraints and interrogate spinal activity during sensory stimulation and motor behaviours. No functional impairment or tissue damage was apparent. Spinotrode recordings allowed identification of distinct functional types of neurons associated with paw withdrawal, revealed dorsal horn activity during locomotor behaviour distinct from proprioception and touch, and uncovered contralateral sensory activation upon nociceptive reflex responses, which forces reassessment of data obtained in anesthetized animals.

neuroscience↗

bioRxiv2025

Deciphering the role of brainstem vestibular-related inhibitory networks in shaping postural reflexes in the Xenopus tadpole

Brainstem vestibulospinal (VS) nuclei generate excitatory commands in response to multi-modality sensory integration, to activate specific spinal networks in order to generate adapted postural reflexes. Comparably organized in bilateral nuclei with both ipsi- and contralateral pathways in all species, excitatory VS projections alone fail to explain the mostly unilateral reflex responses typically observed. In the Xenopus laevis tadpole, we describe secondary vestibular neurons of inhibitory nature, and the synaptic contacts they make on VS neurons. Then, using a brainstem/spinal cord in vitro preparation we show that the spinal responses evoked by galvanic vestibular stimulation are shaped by both commissural and local inhibitory brainstem networks. We further show that a complex interaction between GABAergic and glycinergic inhibitory networks regulate VS neuron excitability and, consequently, the expression of the spinal response. Our data reveal that while excitatory VS neurons execute the neural score, inhibitory neurons in the central vestibular system coordinate and modulate the overall performance.

neuroscience↗

bioRxiv2025

Nucleus raphe magnus serotonin neurons bidirectionally control spinal mechanical pain transmission

BackgroundNoxious stimuli are conveyed to and integrated in the dorsal horn of the spinal cord (DHSC) before being transmitted to supraspinal centers, where pain perception is generated. Descending pathways from the brainstem dynamically modulate this integration, either facilitating or inhibiting nociceptive information based on physiological, emotional, genetic and environmental factors. Serotonergic neurons in the nucleus raphe magnus (NRM), activating different spinal 5-HT receptors, exert bidirectional control, both facilitatory and inhibitory, but the underlying mechanisms of this control remain unclear. MethodsWe investigated in adult mice, the NRM serotonergic modulation of nociception using imaging, behavioral, pharmacological, electrophysiological, chemogenetic and optogenetic approaches. ResultsWe have demonstrated that the action of serotonergic neurons in the NRM on spinal nociceptive transmission depends on their activation pattern, which targets different spinal 5-HT receptors likely associated with different spinal microcircuits. Serotonergic neurons of the NRM exert a tonic analgesic effect mediated by 5-HT2c receptor. Low increase in 5-HT activity leads to an increased analgesia through spinal inhibitory interneurons expressing 5-HT2c and 5-HT2A receptors. Finally, prolonged stimulation of serotonergic neurons led to hyperalgesia mediated by 5-HT3 receptor. Comparison of 5-HT receptors in spinal tissue from mice and human shows that 5-HT2c receptor has a very high expression level, comparable between both species. ConclusionsThese results propose a model of bidirectional action of serotonin neurons on nociceptive transmission depending on their level of activity and show that 5-HT2c receptor is the main mediator of serotonin-induced analgesia.

neuroscience↗

bioRxiv2022

Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior

In threatening situations, animals exhibit a broad range of behavioral and autonomic responses. As such, a crucial adaptive response is the inhibition of pain, which facilitates relevant defensive behaviors that promote survival. Whereas the structures and mechanisms involved in fear and pain behaviors are well documented, little is known about the precise neuronal mechanisms mediating the emotional regulation of endogenous pain-suppression. Here, we used a combination of behavioral, anatomical, optogenetic, and electrophysiological approaches to investigate, in male mice, the role of somatostatin-expressing cells in the ventrolateral periaqueductal gray matter (SST+ vlPAG cells) in the control of analgesia induced during defensive states. Our data indicate that optogenetic inhibition of SST+ vlPAG cells promotes analgesia irrespective of animal defensive state. In contrast, optogenetic activation of long-range SST+ vlPAG cells that project to the rostral ventromedial medulla (RVM) abolishes the analgesia mediated by fear behavior. Together, these results identify a novel circuit mechanism composed of long-range SST+ vlPAG cells projecting to the RVM that regulate analgesia elicited during defensive states.

neuroscience↗