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.

Preventable risk factors for type 2 diabetes can be detected using noninvasive spontaneous electroretinogram signals.

Given the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, and some studies suggested its use for preventable risk factors of type 2 diabetes and thereby diabetic retinopathy (DR). Here, we show that in a non-evoked mode, ERG signals contain spontaneous oscillations that predict disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome but not yet diabetes, using one single random forest-based model.

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.

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.

Focal electrical stimulation on an alcohol disorder model using magnetic resonance imaging-compatible chronic neural monopolar carbon fiber electrodes.

Neuromodulation interventions, such as Deep Brain Stimulation (DBS) and repeated transcranial magnetic stimulation (rTMS), are proposed as possible new complementary therapies to treat substance use disorders (SUD) such as alcohol use disorder (AUD). It is hypothesized that neuromodulation may induce neural plasticity in the reward and frontostriatal systems electrical field induction, possibly reducing symptoms. Preclinical self-administration rodent models of AUD may help us gain insight into the effects of neuromodulation therapies on different pathology, as well as the neural mechanisms behind the positive effects.

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.

Neuronal Glutamatergic Network Electrically Wired with Silent But Activatable Gap Junctions.

It is widely assumed that electrical synapses in the mammalian brain, especially between interneurons, underlie neuronal synchrony. In the hippocampus, principal cells also establish electrical synapses with each other and have also been implicated in network oscillations, whereby the origin of fast electrical activity has been attributed to ectopic spikelets and dendro-dendritic or axo-axonal gap junctions. However, if electrical synapses were in axo-dendritic connections, where chemical synapses occur, the synaptic events would be mixed, having an electrical component preceding the chemical one.

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.

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.

Relationships between structure, in vivo function and long-range axonal target of cortical pyramidal tract neurons.

Pyramidal tract neurons (PTs) represent the major output cell type of the neocortex. To investigate principles of how the results of cortical processing are broadcasted to different downstream targets thus requires experimental approaches, which provide access to the in vivo electrophysiology of PTs, whose subcortical target regions are identified. On the example of rat barrel cortex (vS1), we illustrate that retrograde tracer injections into multiple subcortical structures allow identifying the long-range axonal targets of individual in vivo recorded PTs.

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.

The potential role of serotonergic mechanisms in the spinal oxytocin-induced antinociception.

The role of oxytocin (OXT) in pain modulation has been suggested. Indeed, hypothalamic paraventricular nuclei (PVN) electrical stimuli reduce the nociceptive neuronal activity (i.e.

Sensorimotor Integration by Corticospinal System.

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback.

Hypothalamic paraventricular nucleus stimulation enhances c-Fos expression in spinal and supraspinal structures related to pain modulation.

The hypothalamic paraventricular nuclei (PVN) inhibits spinal nociception. Furthermore, projections from the PVN to other structures related to pain modulation exist, but a functional interaction has not yet been fully demonstrated. As an initial approach, we show here that PVN electric stimulation with the same parameters used to induce analgesia in rats enhances c-Fos expression not only in the dorsal horn of the spinal cord but also in the nucleus raphe magnus, locus coeruleus and the periaqueductal gray area.

Intracisternal injection of palmitoylethanolamide inhibits the peripheral nociceptive evoked responses of dorsal horn wide dynamic range neurons.

Endogenous palmitoylethanolamide (PEA) has a key role in pain modulation. Central or peripheral PEA can reduce nociceptive behavior, but no study has yet reported a descending inhibitory effect on the neuronal nociceptive activity of Aδ- and C-fibers. This study shows that intracisternal PEA inhibits the peripheral nociceptive responses of dorsal horn wide dynamic range cells (i.

The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration.

Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction.

Cortical presynaptic control of dorsal horn C-afferents in the rat.

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents.

Dorsal horn antinociception mediated by the paraventricular hypothalamic nucleus and locus coeruleous: a comparative study.

The noradrenergic descending projection originating in the locus coeruleous (LC), as well as the oxytocinergic descending projection originating in the paraventricular hypothalamic nucleus (PVN), plays a pivotal role in nociception. The mechanisms used by these two systems to modulate synaptic nociceptive transmission in the dorsal horn have been well studied independently. However, little is known about interactions between them.

Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat.

Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C-fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation.

Oxytocin, but not vassopressin, modulates nociceptive responses in dorsal horn neurons.

Oxytocin (OT) and vasopressin (VP) are synthesized and secreted by the paraventricular hypothalamic nucleus (PVN), and both peptides have been implicated in the pain modulatory system. In the spinal cord, activation of OT-containing axons modulates nociceptive neuronal responses in dorsal horn neurons; however, it is not known whether the direct VPergic descending projection participates. Here, we show that both PVN electrical stimulation and topical application of OT in the vicinity of identified and recorded dorsal horn WDR selectively inhibit Adelta and C-fiber responses.

Paraventricular hypothalamic oxytocinergic cells responding to noxious stimulation and projecting to the spinal dorsal horn represent a homeostatic analgesic mechanism.

The participation of the hypothalamic paraventricular nucleus (PVN) in an endogenous central mechanism of analgesia has been observed using rats in various experimental procedures including electrophysiological and behavioral tests. However, little is known about the PVN neuronal responses to noxious stimulation. The only data available indicate a c-fos increase after noxious visceral stimulations.

Paraventricular oxytocinergic hypothalamic prevention or interruption of long-term potentiation in dorsal horn nociceptive neurons: electrophysiological and behavioral evidence.

Spinal long-term potentiation (LTP) elicited by noxious stimulation enhances the responsiveness of dorsal horn nociceptive neurons to their normal input, and may represent a key mechanism of central sensitization by which acute pain could turn into a chronic pain state. This study investigated the electrophysiological and behavioral consequences of the interactions between LTP and descending oxytocinergic antinociceptive mechanisms mediated by the hypothalamic paraventricular nucleus (PVN). PVN stimulation or intrathecal oxytocin (OT) reduced or prevented the ability of spinal LTP to facilitate selectively nociceptive-evoked responses of spinal wide dynamic range (WDR) neurons recorded in anesthetized rats.

Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells.

Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon.

PVN electrical stimulation prolongs withdrawal latencies and releases oxytocin in cerebrospinal fluid, plasma, and spinal cord tissue in intact and neuropathic rats.

We are studying an endogenous, oxytocinergic analgesia system to obtain more information about normal and pathological pain processes. In the recent years, this oxytocinergic system has been shown to be involved in normal and pathological pain suppression. The paraventricular nucleus (PVN) of the hypothalamus is an important source of brain oxytocin (OT).