Biology subjects

Courtand, G.

Publications and source records attributed to Courtand, G..

6 recordsLinked to original sources

bioRxiv2026

Functional maturation in abducens motoneurons populations during angular VOR larval development

Extraocular motoneurons are the final neuronal relay implicated in gaze motor control and are known to be subdivided in functional subgroups, differently implicated in ocular motion dynamics. However, the maturation of these functional populations of extraocular motoneurons, in relation with the development of gaze-stabilizing reflexes remains largely unexplored. In amphibian tadpoles, the angular vestibulo-ocular reflex (VOR) appears later than other visuo-vestibular ocular reflexes and matures until the metamorphosis climax. Two types of Abducens motoneurons have been described to participate to the angular VOR in larval frog: spontaneous motor units, exhibiting a robust resting activity and silent motor units recruited only during head motion. The aim of this study was to investigate the maturation of these two types of Abducens motor units in relation with the development of the angular VOR by evaluating their discharge dynamic in response to head rotation in semi-intact preparations of larval Xenopus laevis. During larval life, the discharge modulation during sinusoidal head rotations increases significantly for silent units only, demonstrating a better sensitivity of this Abducens motoneuron sub-population to horizontal semicircular canal activation. In addition, this functional maturation was accompanied by an increase of the myelination in the lateral rectus motor nerve, promoting a faster conductivity in late larval stages than in early one. These findings showed that the development of the angular VOR is supported by a selective maturation of extraocular motoneurons subpopulations, specifically implicated in the improvement of the ocular kinematic during the reflex.

neuroscience↗

bioRxiv2024

Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease.

Huntingtons disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the gene encoding the Huntingtin protein (Htt). While symptoms, primarily characterized by progressive deterioration of the striatum and motor and cognitive functions, typically manifest in adulthood, recent studies have also highlighted developmental defects in HD. Indeed, alterations in cortical and striatal development have been observed in individuals carrying the mutation as early as in embryonic stages. However, despite the striatum being one of the most affected regions in HD, few studies have investigated potential developmental alterations in this structure, especially in the early weeks after birth. To address this question, we compared striatal development between wild-type (WT) mice and two murine models of HD, R6/1 and CAG140 mice crossed with reporter mice to identify D1- and D2-expressing medium spiny neurons (D1- and D2-MSNs). Using ex vivo electrophysiology and neuronal reconstruction, we observed that the maturation of electrical properties was selectively disrupted in D2-MSNs of the matrix compartment of HD mice during the first post-natal days. D2-MSNs arbor also an increased dendritic complexity. When studying the establishment of striatal afferents, we observed that cortico-striatal glutamatergic transmission was specifically reduced in D2-MSNs during the second postnatal week. All these alterations were transient before the circuit normalized on its own after the second postnatal week. These anatomical and electrophysiological data highlight the significant impact of the Htt mutation on numerous striatal development processes during the postnatal period. Interestingly, we observed that these alterations specifically affect MSNs in the indirect pathway. This preferential vulnerability aligns with the early death of these neurons in adulthood, suggesting that early treatment of these alterations could potentially modify the diseases progression.

neuroscience↗

bioRxiv2022

Microglia shape the embryonic development of mammalian respiratory networks

Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT, Pu.1+/+) mouse brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preBotzinger complex (preBotC)). In transgenic mice depleted of microglia (Pu.1-/- mutant), we performed anatomical staining, calcium imaging and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preBotC at E16.5 and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preBotC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5 Pu.1-/- embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development.

neuroscience↗

bioRxiv2021

Conservation of locomotion-induced oculomotor activity through evolution in higher tetrapods

Efference copies are neural replicas of motor outputs used to anticipate the sensory consequences of a self-generated motor action or to coordinate neural networks involved in distinct motor behaviors1. An established example of this motor-to-motor coupling is the efference copy of the propulsive motor command that supplements classical visuo-vestibular reflexes to ensure gaze stabilization during amphibian larval locomotion2. Such feedforward replica from spinal pattern-generating circuits produces a spino-extraocular motor coupled activity that evokes eye movements, spatio-temporally coordinated to tail undulation independently of any sensory signal3,4. Exploiting the evolutionary-development characteristic of the frog1, studies in metamorphing Xenopus demonstrated the persistence of this spino-extraocular motor command in adults, and its developmental adaptation to tetrapodal locomotion5,6. Here, we demonstrate for the first time the existence of a comparable locomotor-to-ocular motor coupling in the mouse. In neonates, ex vivo nerve recordings from brainstem-spinal cord preparation reveals a spino-extraocular motor coupled activity similar to the one described in Xenopus. In adult mice, trans-synaptic rabies injection in lateral rectus eye muscle labels cervical spinal cord neurons projecting directly to abducens motor neurons. Finally, treadmill-elicited locomotion in decerebrated preparations7 evokes rhythmic eye movements in synchrony with the limb gait pattern. Overall, our data are evidence for the conservation of locomotor-induced eye movements in higher tetrapods. Thus, in mammals as in amphibians, during locomotion CPG-efference copy feedforward signals might interact with sensory feedback to ensure efficient gaze control. HighlightsO_LISpino-extraocular motor coupling is evidenced from newborn mice ex vivo preparations C_LIO_LIAdult decerebrated mice exhibit conjugated rhythmic eye movements during treadmill locomotion C_LIO_LILocomotor-induced oculomotor activity occurs in absence of visuo-vestibular inputs C_LIO_LIConserved CPG-based efference copy signal in vertebrates with common features. C_LI eTOC blurbWe report a functional coupling between spinal locomotor and oculomotor networks in the mouse, similar to the one previously described in Amphibians. This is the first evidence for the direct contribution of locomotor networks to gaze control in mammals, suggesting a conservation of the spino-extraocular coupling in higher tetrapods during sustained locomotion.

neuroscience↗

bioRxiv2021

Locomotion-induced ocular motor behavior in larval Xenopus is developmentally tuned by visuo-vestibular reflexes

Locomotion requires neural computations to maintain stable perception of the world despite disturbing consequences of the motor behavior on sensory stability. The developmental establishment of locomotor proficiency is therefore accompanied by a concurrent maturation of gaze-stabilizing motor behaviors. Using developing larval Xenopus, we demonstrate mutual plasticity of predictive spinal locomotor efference copies and multi-sensory motion signals with the aim to constantly ensure dynamically adequate eye movements during swimming. Following simultaneous ontogenetic onsets of locomotion, spino-ocular, optokinetic and otolith-ocular motor behaviors, locomotor efference copy-driven eye movements improve through gradually augmenting influences of semicircular canal signals. Accordingly, neuronal computations change from a predominating cancelation of angular vestibulo-ocular reflexes by locomotor efference copies in young larvae to a summation of these signals in older larvae. The developmental switch occurs in synchrony with a reduced efficacy of the tail-undulatory locomotor pattern generator causing gradually decaying influences on the ocular motor output.

neuroscience↗

bioRxiv2020

A disynaptic circuit in the globus pallidus controls locomotion inhibition

Basal ganglia (BG) inhibit movement through two independent pathways, the indirect- and the hyperdirect-pathways. The globus pallidus (GP) has always been viewed as a simple relay within these two pathways, but its importance has changed drastically with the discovery of two functionally-distinct cell types, namely the prototypic and the arkypallidal neurons. Classic BG models suggest that all GP neurons receive GABAergic inputs from striato-pallidal indirect spiny projection neurons and glutamatergic inputs from subthalamic neurons. However, whether this synaptic connectivity scheme applies to both GP cell-types is currently unknown. Here, we optogenetically dissect the input organization of prototypic and arkypallidal neurons and further define the circuit mechanism underlying action inhibition in BG. Our results highlight that an increased activity of arkypallidal neurons is required to inhibit locomotion. Finally, this work supports the view that arkypallidal neurons are part of a novel disynaptic feedback loop that broadcast inhibitory control on movement execution.

neuroscience↗