Modulation of Respiratory System by Limb Muscle Afferents in Intact and Injured Spinal Cord.

Breathing constantly adapts to environmental, metabolic or behavioral changes by responding to different sensory information, including afferent feedback from muscles. Importantly, not just respiratory muscle feedback influences respiratory activity. Afferent sensory information from rhythmically moving limbs has also been shown to play an essential role in the breathing.

Transplantation of Neural Progenitors and V2a Interneurons after Spinal Cord Injury.

There is growing interest in the use of neural precursor cells to treat spinal cord injury (SCI). Despite extensive pre-clinical research, it remains unclear as to which donor neuron phenotypes are available for transplantation, whether the same populations exist across different sources of donor tissue (e.g.

Paced breathing and phrenic nerve responses evoked by epidural stimulation following complete high cervical spinal cord injury in rats.

Spinal cord injury (SCI) at the level of cervical segments often results in life-threatening respiratory complications and requires long-term mechanical ventilator assistance. Thus restoring diaphragm activity and regaining voluntary control of breathing are the primary clinical goals for patients with respiratory dysfunction following cervical SCI. Epidural stimulation (EDS) is a promising strategy that has been explored extensively for nonrespiratory functions and to a limited extent within the respiratory system.

Spontaneous respiratory plasticity following unilateral high cervical spinal cord injury in behaving rats.

Unilateral cervical C2 hemisection (C2Hx) is a classic model of spinal cord injury (SCI) for studying respiratory dysfunction and plasticity. However, most previous studies were performed under anesthesia, which significantly alters respiratory network. Therefore, the goal of this work was to assess spontaneous diaphragm recovery post-C2Hx in awake, freely behaving animals.

Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord.

Cervical spinal cord injuries (SCI) result in devastating functional consequences, including respiratory dysfunction. This is largely attributed to the disruption of phrenic pathways, which control the diaphragm. Recent work has identified spinal interneurons as possible contributors to respiratory neuroplasticity.

Supraspinal respiratory plasticity following acute cervical spinal cord injury.

Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the diaphragm - a primary muscle of respiration. Consequently, people with cervical level injuries often become dependent on assisted ventilation and are susceptible to secondary complications. However, there is mounting evidence for limited spontaneous recovery of respiratory function following injury, demonstrating the neuroplastic potential of respiratory networks.

Histological identification of phrenic afferent projections to the spinal cord.

Limited data are available regarding the spinal projections of afferent fibers in the phrenic nerve. We describe a method that robustly labels phrenic afferent spinal projections in adult rats. The proximal end of the cut phrenic nerve was secured in a microtube filled with a transganglionic tracer (cholera toxin β-subunit, CT-β, or Cascade Blue) and tissues harvested 96-h later.

Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury.

Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals.

Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Bötzinger and Bötzinger Complexes.

The pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes are the brainstem compartments containing interneurons considered to be critically involved in generating respiratory rhythm and motor pattern in mammals. Current models postulate that both generation of the rhythm and coordination of the inspiratory-expiratory pattern involve inhibitory synaptic interactions within and between these regions. Both regions contain glycinergic and GABAergic neurons, and rhythmically active neurons in these regions receive appropriately coordinated phasic inhibition necessary for generation of the normal three-phase respiratory pattern.

Modulation of artificial whisking related signals in barrel cortex.

Rats use rhythmic whisker movements, called active whisking, to sense the environment, which include whisker protractions followed by retractions at various frequencies. Using a proxy of active whisking in anesthetized rats, called artificial whisking, which is induced by electrically stimulating the facial motor nerve, we characterized the neural responses evoked in the barrel cortex by whisking in air (without contact) and on a surface (with contact). Neural responses were compared between distinct network states consisting of cortical deactivation (synchronized slow oscillations) and activation (desynchronized state) produced by neuromodulation (cholinergic or noradrenergic stimulation in neocortex or thalamus).

Interdisciplinary approaches of transcranial magnetic stimulation applied to a respiratory neuronal circuitry model.

Respiratory related diseases associated with the neuronal control of breathing represent life-threatening issues and to date, no effective therapeutics are available to enhance the impaired function. The aim of this study was to determine whether a preclinical respiratory model could be used for further studies to develop a non-invasive therapeutic tool applied to rat diaphragmatic neuronal circuitry. Transcranial magnetic stimulation (TMS) was performed on adult male Sprague-Dawley rats using a human figure-of-eight coil.

Neuromodulation of whisking related neural activity in superior colliculus.

The superior colliculus is part of a broader neural network that can decode whisker movements in air and on objects, which is a strategy used by behaving rats to sense the environment. The intermediate layers of the superior colliculus receive whisker-related excitatory afferents from the trigeminal complex and barrel cortex, inhibitory afferents from extrinsic and intrinsic sources, and neuromodulatory afferents from cholinergic and monoaminergic nuclei. However, it is not well known how these inputs regulate whisker-related activity in the superior colliculus.

Superior colliculus cells sensitive to active touch and texture during whisking.

Rats sense the environment through rhythmic vibrissa protractions, called active whisking, which can be simulated in anesthetized rats by electrically stimulating the facial motor nerve. Using this method, we investigated barrel cortex field potential and superior colliculus single-unit responses during passive touch, whisking movement, active touch, and texture discrimination. Similar to passive touch, whisking movement is signaled during the onset of the whisker protraction by short-latency responses in barrel cortex that drive corticotectal responses in superior colliculus, and all these responses show robust adaptation with increases in whisking frequency.

Laterodorsal nucleus of the thalamus: A processor of somatosensory inputs.

The laterodorsal (LD) nucleus of the thalamus has been considered a "higher order" nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information.

Encoding of stimulus frequency and sensor motion in the posterior medial thalamic nucleus.

In all sensory systems, information is processed along several parallel streams. In the vibrissa-to-barrel cortex system, these include the lemniscal system and the lesser-known paralemniscal system. The posterior medial nucleus (POm) is the thalamic structure associated with the latter pathway.

Brain state and contrast sensitivity in the awake visual thalamus.

Neuronal responses to visual stimuli depend on both the nature of the stimulus and brain state. Here we examined the contrast sensitivity of visual thalamic neurons as awake rabbits shifted between alert and nonalert states. We found that despite a large increase in response gain with alertness, contrast sensitivity remained nearly constant.

Cholinergic regulation of the posterior medial thalamic nucleus.

We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep-wake cycles and states of vigilance.

The impact of a corticotectal impulse on the awake superior colliculus.

Corticotectal (CTect) neurons of layer 5 are large and prominent elements of mammalian visual cortex, with thick apical dendrites that ascend to layer 1, "intrinsically bursting" membrane properties, and fast-conducting descending axons that terminate in multiple subcortical domains. These neurons comprise a major output pathway of primary visual cortex, but virtually nothing is known about the synaptic influence of single CTect impulses on the superior colliculus (SC). Here, we examine the distribution of monosynaptic currents generated in the superficial SC by spontaneous impulses of single CTect neurons.

Thalamic burst mode and inattention in the awake LGNd.

Awake mammals are often inattentive in familiar environments, but must still respond appropriately to relevant visual stimulation. Such "inattentive vision" has received little study, perhaps due to difficulties in controlling eye position in this state. In rabbits, eye position is exceedingly stable in both alert and inattentive states.

Spike timing and synaptic dynamics at the awake thalamocortical synapse.

Thalamocortical (TC) neurons form only a small percentage of the synapses onto neurons of cortical layer 4, but the response properties of these cortical neurons are arguably dominated by thalamic input. This discrepancy is explained, in part, by studies showing that TC synapses are of high efficacy. However, TC synapses display activity-dependent depression.

A multi-channel, implantable microdrive system for use with sharp, ultra-fine "Reitboeck" microelectrodes.

Arrays of closely spaced quartz-insulated, platinum-tungsten microelectrodes are widely used to obtain acute recordings from chronically prepared subjects. These electrodes have excellent recording characteristics and can be fabricated to a wide variety of tip specifications. Typically, in such experiments, electrodes are introduced into, and removed from, the brain on a daily basis and, over many months of study, hundreds of penetrations may be made through an intact dura.

Activation of a cortical column by a thalamocortical impulse.

Thalamocortical (TC) impulses potently influence the sensory neocortex, but the functional impact of individual TC neurons throughout the layers of the cortex has proved difficult to assess. Here we examine, in awake rabbits, the vertical distribution of monosynaptic currents generated in a somatosensory cortical "barrel" column by spontaneous impulses of single, topographically aligned TC neurons. We show that closely neighboring TC neurons generate widely differing patterns of monosynaptic activation within layers 4 and 6 of their aligned column.