Motor cortex projections to red and pontine nuclei have distinct roles during movement in the mouse.

Motor control largely depends on the deep layer 5 (L5) pyramidal neurons that project to subcortical structures. However, it is largely unknown if these neurons are functionally segregated with distinct roles in movement performance. Here, we analyzed mouse motor cortex L5 pyramidal neurons projecting to the red and pontine nuclei during movement preparation and execution. Using photometry to analyze the calcium activity of L5 pyramidal neurons projecting to the red nucleus and pons, we reveal that both types of neurons activate with different temporal dynamics. Optogenetic inhibition of either kind of projection differentially affects forelimb movement onset and execution in a lever press task, but only the activity of corticopontine neurons is significantly correlated with trial-by-trial variations in reaction time. The results indicate that cortical neurons projecting to the red and pontine nuclei contribute differently to sensorimotor integration, suggesting that L5 output neurons are functionally compartmentalized generating, in parallel, different downstream information.

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.

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.

Phosphorylation of Tau protein correlates with changes in hippocampal theta oscillations and reduces hippocampal excitability in Alzheimer's model.

Tau hyperphosphorylation at several sites, including those close to the microtubule domain region (MDr), is considered a key pathological event in the development of Alzheimer's disease (AD). Recent studies indicate that at the very early stage of this disease, increased phosphorylation in Tau's MDr domain correlates with reduced levels of neuronal excitability. Mechanistically, we show that pyramidal neurons and some parvalbumin-positive interneurons in 1-month-old triple-transgenic AD mice accumulate hyperphosphorylated Tau protein and that this accumulation correlates with changes in theta oscillations in hippocampal neurons. Pyramidal neurons from young triple-transgenic AD mice exhibited less spike accommodation and power increase in subthreshold membrane oscillations. Furthermore, triple-transgenic AD mice challenged with the potassium channel blocker 4-aminopyridine had reduced theta amplitude compared with 4-aminopyridine-treated control mice and, unlike these controls, displayed no seizure-like activity after this challenge. Collectively, our results provide new insights into AD pathogenesis and suggest that increases in Tau phosphorylation at the initial stages of the disease represent neuronal responses that compensate for brain circuit overexcitation.

Hemangioma cavernoso sublingual / Sublingual cavernous haemanginoma

No disponible

Historia familiar con síndrome de Brugada: a propósito de un caso / Family history with Brugada's syndrome: a case report

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