Biology subjects

Laliberte, A. M.

Publications and source records attributed to Laliberte, A. M..

4 recordsLinked to original sources

bioRxiv2025

Spinal dI3 neurons are involved in sustained motor adaptation elicited by low-threshold cutaneous afferents

Adaptation of muscle activity to meet a certain target or intention is traditionally attributed to supraspinal structures. However, evidence is mounting that this process can occur within the spinal cord through intrinsic plasticity and circuit reorganization. Here, we investigate the role of a class of excitatory spinal interneurons, called dorsal interneuron 3 (dI3), in the acquisition of novel motor behaviors independent of supraspinal input. Using a real-time closed-loop stimulation paradigm in spinalized mice, we promoted a persistent adaptation in the hindlimb position to be higher than its resting level by delivering saphenous nerve stimulation contingent on toe elevation. The stimulation intensities were calibrated to selectively recruit low-threshold mechanoreceptors (LTMRs). To test the contribution of dI3s in this motor adaptation, inhibitory DREADD (hM4Di) receptors were expressed in Isl1/Vglut2 cells, achieving reversible, cell-type-specific silencing of dI3s. Our results demonstrate that stimulation of cutaneous inputs to the spinal cord contingent on a certain positional goal can generate sustained changes in motor activity, in this case, in the form of elevation of toe position above a preset vertical threshold. Chemogenetic silencing of dI3s abolished this motor adaptation induced by activation of LTMRs. These findings indicate that dI3 activity is essential for a particular type of motor adaptation driven primarily by LTMR input. NEW & NOTEWORTHYWe developed a real-time, closed-loop stimulation paradigm in spinalized mice using kinematic video tracking to trigger electrical stimulation of the saphenous nerve. We discovered that low-threshold stimulations targeting non-nociceptive cutaneous afferents can elicit sustained motor adaptations independently from supraspinal input. Furthermore, using two chemogenetic techniques to transiently inhibit a population of spinal neurons, called dI3s, we found that these neurons are crucial for integrating these low-threshold stimuli to elicit sustained changes in motor behaviour.

neuroscience↗

bioRxiv2025

Altered excitability of dI3 neurons regulates hindlimb motor tone and locomotor recovery after spinal cord injury

Recovery of motor function after spinal cord injury is limited in mammals. Reactivation of locomotor circuits does occur, but primarily through the activation of sensorimotor pathways in the context of locomotor training. Previous investigations have shown that dI3 neurons, a developmentally-defined population of pre-motor, glutamatergic interneurons, are indispensable for this process. However, it remains unclear how dI3 neurons are recruited during locomotor recovery, and whether they could be leveraged to improve locomotor function following spinal cord injury. Herein, we investigated how the excitability of dI3 neurons influences locomotor behaviour and recovery after spinal cord injury. In T9-T10 transected mice, we found that acute chemogenetic silencing of dI3 neurons leads to immediate loss of hindlimb motor tone, and significant reduction in stepping during treadmill locomotion. Conversely, regular chemogenetic stimulation of dI3 neurons led to transient increases in hindlimb motor tone early after injury, but ultimately reduced hindlimb motor tone and locomotor recovery over the long term. These chronic changes resulting from dI3 neuron stimulation were associated with the absence of expression of the constitutive 5-HT2C-R isoform, potentially representing a homeostatic mechanism for the regulation of dI3 excitability following spinal cord injury. Given these findings, we hypothesized that dI3 stimulations effects on motor tone, while insufficient to drive locomotor function alone, may promote stepping improvements when locomotor rhythm-generating circuits are active. The addition of quipazine, a serotonergic agonist known to facilitate locomotor rhythmogenesis, in combination with dI3 stimulation, significantly improved locomotor function, while also mitigating the long-term reduction in treadmill stepping associated with dI3 stimulation alone. In aggregate, our results suggest that hyper-excitable dI3 neurons are involved in the maintenance of motor tone after spinal cord injury, possibly through a 5-HT2C-R-dependent mechanism, and further show that the selective stimulation of dI3 neurons could enhance the recovery of locomotor function following spinal cord injury.

neuroscience↗

bioRxiv2025

Evidence of spinal cord comparator modules for rapid corrections of movements

Successful movement requires continuous adjustments in response to changes in internal and external environments. To do so, neural circuits continuously compare efference copies of motor commands with sensory feedback to respond to sensory prediction errors. Some responses need to be very fast, indicating that they likely occur within spinal cord circuits. Here, we describe spinal cord circuits involving dI3 neurons, showing that they receive multimodal sensory inputs and direct efferent copies from both Renshaw cells and motor neurons. We further show that they form connections to motor pools. Reducing dI3 neuronal activity diminished stumbling responses, as did disrupting Renshaw cell circuits, providing evidence for a comparator role of dI3 neurons for online corrections. Together, our findings reveal a pivotal role for dI3 neurons functioning as comparators of efference copies and external sensory feedback to mediate rapid corrections of ongoing movements.

neuroscience↗

bioRxiv2024

Mapping of dI3 neuron sensorimotor circuits across the cervical and lumbar spinal cord

From the fine control of hand movements to the dynamic corrective adjustments during locomotion, spinal circuits integrate descending supraspinal and sensory inputs to modulate diverse motor functions. The integration of such a wide range of signals across the spinal cord is primarily mediated by propriospinal interneurons. In this study, we investigate the connectivity of a population of propriospinal interneurons marked by the expression of Isl1, called dI3 neurons. These dI3s integrate supraspinal and sensory signals to facilitate many important functions, such as hand grasp, locomotion, and motor recovery after spinal cord injury; however, we have a limited understanding of how subpopulations of dI3s modulate network activity across the spinal cord to contribute to these behaviors. Their functional connectivity to motor circuits across the cervical and lumbar spinal cord was assessed through optogenetic activation of dI3s localized in different spinal segments. Our data demonstrates that cervical and lumbar dI3 subpopulations can form local, commissural, intersegmental, and long propriospinal pathways. Furthermore, dI3 subpopulations can be tonically stimulated to elicit locomotor activity. These extensive projection patterns of dI3s across the cervical and lumbar spinal cord suggest that dI3 subpopulations can modulate the activity of multiple motor networks within their respective spinal cord segments or across distant forelimb and hindlimb segments to facilitate a wide variety of motor functions.

neuroscience↗