Corticospinal neurons from motor and somatosensory cortices exhibit different temporal activity dynamics during motor learning.

The ability to learn motor skills implicates an improvement in accuracy, speed and consistency of movements. Motor control is related to movement execution and involves corticospinal neurons (CSp), which are broadly distributed in layer 5B of the motor and somatosensory cortices. CSp neurons innervate the spinal cord and are functionally diverse. However, whether CSp activity differs between different cortical areas throughout motor learning has been poorly explored. Given the importance and interaction between primary motor (M1) and somatosensory (S1) cortices related to movement, we examined the functional roles of CSp neurons in both areas. We induced the expression of GCaMP7s calcium indicator to perform photometric calcium recordings from layer 5B CSp neurons simultaneously in M1 and S1 cortices and track their activity while adult mice learned and performed a cued lever-press task. We found that during early learning sessions, the population calcium activity of CSp neurons in both cortices during movement did not change significantly. In late learning sessions the peak amplitude and duration of calcium activity CSp neurons increased in both, M1 and S1 cortices. However, S1 and M1 CSp neurons display a different temporal dynamic during movements that occurred when animals learned the task; both M1 and S1 CSp neurons activate before movement initiation, however, M1 CSp neurons continue active during movement performance, reinforcing the idea of the diversity of the CSp system and suggesting that CSp neuron activity in M1 and S1 cortices throughout motor learning have different functional roles for sensorimotor integration.

Different subtypes of motor cortex pyramidal tract neurons projects to red and pontine nuclei.

Introduction: Pyramidal tract neurons (PTNs) are fundamental elements for motor control. However, it is largely unknown if PTNs are segregated into different subtypes with distinct characteristics. Methods: Using anatomical and electrophysiological tools, we analyzed in mice motor cortex PTNs projecting to red and pontine midbrain nuclei, which are important hubs connecting cerebral cortex and cerebellum playing a critical role in the regulation of movement. Results: We reveal that the vast majority of M1 neurons projecting to the red and pontine nuclei constitutes different populations. Corticopontine neurons have higher conduction velocities and morphologically, a most homogeneous dendritic and spine distributions along cortical layers. Discussion: The results indicate that cortical neurons projecting to the red and pontine nuclei constitute distinct anatomical and functional pathways which may contribute differently to sensorimotor integration.

NMDA Receptor Hypofunction in the Aging-Associated Malfunction of Peripheral Tissue.

Glutamatergic transmission through NMDA receptors (NMDARs) is important for the function of peripheral tissues. In the bone, NMDARs and its co-agonist, D-serine participate in all the phases of the remodeling. In the vasculature, NMDARs exerts a tonic vasodilation decreasing blood perfusion in the corpus cavernosum and the filtration rate in the renal glomerulus. NMDARs are relevant for the skin turnover regulating the proliferation and differentiation of keratinocytes and the formation of the cornified envelope (CE). The interference with NMDAR function in the skin leads to a slow turnover and repair. As occurs with the brain and cognitive functions, the manifestations of a hypofunction of NMDARs resembles those observed during aging. This raises the question if the deterioration of the glomerular vasculature, the bone remodeling and the skin turnover associated with age could be related with a hypofunction of NMDARs. Furthermore, the interference of D-serine and the effects of its supplementation on these tissues, suggest that a decrease of D-serine could account for this hypofunction pointing out D-serine as a potential therapeutic target to reduce or even prevent the detriment of the peripheral tissue associated with aging.

Corticospinal vs Rubrospinal Revisited: An Evolutionary Perspective for Sensorimotor Integration.

The knowledge about how different subsystems participate and interplay in sensorimotor control is fundamental to understand motor deficits associated with CNS injury and movement recovery. The role of corticospinal (CS) and rubrospinal (RS) projections in motor control has been extensively studied and compared, and it is clear that both systems are important for skilled movement. However, during phylogeny, the emerging cerebral cortex took a higher hierarchical role controlling rubro-cerebellar circuits. Here, we present anatomical, neurophysiological, and behavioral evidence suggesting that both systems modulate complex segmental neuronal networks in a parallel way, which is important for sensorimotor integration at spinal cord level. We also highlight that, although specializations exist, both systems could be complementary and potentially subserve motor recovery associated with CNS damage.

Operant conditioning paradigm for juxtacellular recordings in functionally identified cortical neurons during motor execution in head-fixed rats.

BACKGROUND: Understanding the configuration of neural circuits and the specific role of distinct cortical neuron types involved in behavior, requires the study of structure-function and connectivity relationships with single cell resolution in awake behaving animals. Despite head-fixed behaving rats have been used for in vivo measuring of neuronal activity, it is a concern that head fixation could change the performance of behavioral task. NEW METHOD: We describe the procedures for efficiently training Wistar rats to develop a behavioral task, involving planning and execution of a qualified movement in response to a visual cue under head-fixed conditions. The behavioral and movement performance in freely moving vs head-fixed conditions was analyzed. RESULTS: The best behavioral performance was obtained in the rats that were trained first in freely moving conditions and then placed in a head-restrained condition compared with the animals which first were habituated to head-restriction and then learned the task. Moreover, head restriction did not alter the movement performance. Stable juxtacellular recordings from sensorimotor cortex neurons were obtained while the rats were performing forelimb movements. Biocytin electroporation and retrograde tracer injections, permits identify the hodology of individual long-range projecting neurons. COMPARISON WITH EXISTING METHODS: Our method shows no difference in the behavioral performance of head fixed and freely moving conditions. Also includes a computer aided design of a discrete and ergonomic head-post allowing enough stability to perform juxtacellular recording and labeling of cortical neurons. CONCLUSIONS: Our method is suitable for the in vivo characterization of neuronal circuits and their long-range connectivity.

Mouse corticospinal system comprises different functional neuronal ensembles depending on their hodology.

BACKGROUND: Movement performance depends on the synaptic interactions generated by coherent parallel sensorimotor cortical outputs to different downstream targets. The major outputs of the neocortex to subcortical structures are driven by pyramidal tract neurons (PTNs) located in layer 5B. One of the main targets of PTNs is the spinal cord through the corticospinal (CS) system, which is formed by a complex collection of distinct CS circuits. However, little is known about intracortical synaptic interactions that originate CS commands and how different populations of CS neurons are functionally organized. To further understand the functional organization of the CS system, we analyzed the activity of unambiguously identified CS neurons projecting to different zones of the same spinal cord segment using two-photon calcium imaging and retrograde neuronal tracers. RESULTS: Sensorimotor cortex slices obtained from transgenic mice expressing GCaMP6 funder the Thy1 promoter were used to analyze the spontaneous calcium transients in layer 5 pyramidal neurons. Distinct subgroups of CS neurons projecting to dorsal horn and ventral areas of the same segment show more synchronous activity between them than with other subgroups. CONCLUSIONS: The results indicate that CS neurons projecting to different spinal cord zones segregated into functional ensembles depending on their hodology, suggesting that a modular organization of CS outputs controls sensorimotor behaviors in a coordinated manner.

The rat corticospinal system is functionally and anatomically segregated.

The descending corticospinal (CS) projection has been considered a key element for motor control, which results from direct and indirect modulation of spinal cord pre-motor interneurons in the intermediate gray matter of the spinal cord, which, in turn, influences motoneurons in the ventral horn. The CS tract (CST) is also involved in a selective and complex modulation of sensory information in the dorsal horn. However, little is known about the spinal network engaged by the CST and the organization of CS projections that may encode different cortical outputs to the spinal cord. This study addresses the issue of whether the CS system exerts parallel control on different spinal networks, which together participate in sensorimotor integration. Here, we show that in the adult rat, two different and partially intermingled CS neurons in the sensorimotor cortex activate, with different time latencies, distinct spinal cord neurons located in the dorsal horn and intermediate zone of the same segment. The fact that different populations of CS neurons project in a segregated manner suggests that CST is composed of subsystems controlling different spinal cord circuits that modulate motor outputs and sensory inputs in a coordinated manner.