GABA and IA Independently Regulate rNST Responses to Afferent Input

Taste responses in the rostral nucleus of the solitary tract (rNST) influence motivated ingestive behavior via ascending pathways, and consummatory reflex behavior via local, brainstem connections. Modifications to the afferent signal within the rNST include changes in gain (the overall rate of neuron activity) and changes in gustatory tuning (the degree to which individual neurons respond to divergent gustatory qualities). These alterations of the sensory signal derive from both synaptic interactions within the nucleus and the constitutive cellular membrane properties of rNST neurons. GABA neurons are well represented within the rNST, as is expression of KV4.3, a channel for a rapidly inactivating outward K+ current (IA). GABAergic synapses suppress rNST responses to afferent input and previous studies showed that this suppression is greater in cells expressing IA, suggesting a possible interaction. Here, we examine the potential interaction between GABAergic inhibition and IA channels in a series of patch clamp experiments. Optogenetic release of GABA suppressed rNST responses to afferent (electrical) stimulation and this effect was greater in cells with IA, confirming an earlier report. We further observed that the composite inhibitory postsynaptic potential was larger in IA positive cells, suggesting one mechanism for the greater afferent suppression. Blocking IA with the channel blocker AmmTX3, enhanced the response to afferent stimulation, suggesting a suppressive role for this channel in regulating afferent input at rest. However, pharmacologic blockade of IA did not suppress GABAergic inhibition, indicating that IA and GABA independently regulate excitatory afferent input.

Orofacial Neuropathic Pain-Basic Research and Their Clinical Relevancies

Trigeminal nerve injury is known to cause severe persistent pain in the orofacial region. This pain is difficult to diagnose and treat. Recently, many animal studies have reported that rewiring of the peripheral and central nervous systems, non-neuronal cell activation, and up- and down-regulation of various molecules in non-neuronal cells are involved in the development of this pain following trigeminal nerve injury. However, there are many unknown mechanisms underlying the persistent orofacial pain associated with trigeminal nerve injury. In this review, we address recent animal data regarding the involvement of various molecules in the communication of neuronal and non-neuronal cells and examine the possible involvement of ascending pathways in processing pathological orofacial pain. We also address the clinical observations of persistent orofacial pain associated with trigeminal nerve injury and clinical approaches to their diagnosis and treatment.

Differential role of spinal and supraspinal processing of proprioceptive information in mouse locomotion

Safe locomotion relies on information from proprioceptors, sensory organs that communicate the position of body parts to the central nervous system. Proprioceptive circuits in the spinal cord are known to robustly regulate locomotion in challenging environments. The role of ascending pathways conveying proprioceptive information to the brain remains less clear. Through mouse genetic studies and in vivo electrophysiology, here we show that the systemic removal of proprioceptors leaves the animals in a constantly perturbed state, similar to that observed during mechanically perturbed locomotion in wild type. Yet, after surgical interruption of the ascending proprioceptive pathways, wild-type mice lose the ability to cope with external perturbations while walking. Our findings provide direct evidence of a pivotal role for ascending proprioceptive information in achieving safe locomotion.

Circuit organization of the excitatory sensorimotor loop through hand/forelimb S1 and M1

Sensory-guided limb control relies on communication across sensorimotor loops. For active touch with the hand, the longest loop is the transcortical continuation of ascending pathways, particularly the lemnisco-cortical and corticocortical pathways carrying tactile signals via the cuneate nucleus, ventral posterior lateral (VPL) thalamus, and primary somatosensory (S1) and motor (M1) cortices to reach corticospinal neurons and influence descending activity. We characterized excitatory connectivity along this pathway in the mouse. In the lemnisco-cortical leg, disynaptic cuneate→VPL→S1 connections excited mainly layer (L) 4 neurons. In the corticocortical leg, S1→M1 connections from L2/3 and L5A neurons mainly excited downstream L2/3 neurons, which excite corticospinal neurons. The findings provide a detailed new wiring diagram for the hand/forelimb-related transcortical circuit, delineating a basic but complex set of cell-type-specific feedforward excitatory connections that selectively and extensively engage diverse intratelencephalic projection neurons, thereby polysynaptically linking subcortical somatosensory input to cortical motor output to spinal cord.

Neural Processing of Pain and Itch

Pain is defined as “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage,” while itch can be defined as “an unpleasant sensation that evokes the desire to scratch.” These sensations are normally elicited by noxious or pruritic stimuli that excite peripheral sensory neurons connected to spinal circuits and ascending pathways involved in sensory discrimination, emotional aversiveness, and respective motor responses. Specialized molecular receptors expressed by cutaneous nerve endings transduce stimuli into action potentials conducted by C- and Aδ-fiber nociceptors and pruriceptors into the outer lamina of the dorsal horn of the spinal cord. Here, neurons selectively activated by nociceptors, or by convergent input from nociceptors, pruriceptors, and often mechanoreceptors, transmit signals to ascending spinothalamic and spinoparabrachial pathways. The spinal circuitry for itch requires interneurons expressing gastrin-releasing peptide and its receptor, while spinal pain circuitry involves other excitatory neuropeptides; both itch and pain are transmitted by ascending pathways that express the receptor for substance P. Spinal itch- and pain-transmitting circuitry is segmentally modulated by inhibitory interneurons expressing dynorphin, GABA, and glycine, which mediate the antinociceptive and antipruritic effects of noxious counterstimulation. Spinal circuits are also under descending modulation from the brainstem rostral ventromedial medulla. Opioids like morphine inhibit spinal pain-transmitting circuits segmentally and via descending inhibitory pathways, while having the opposite effect on itch. The supraspinal targets of ascending pain and itch pathways exhibit extensive overlap and include the somatosensory thalamus, parabrachial nucleus, amygdala, periaqueductal gray, and somatosensory, anterior cingulate, insular, and supplementary motor cortical areas. Following tissue injury, enhanced pain is evoked near the injury (primary hyperalgesia) due to release of inflammatory mediators that sensitize nociceptors. Within a larger surrounding area of secondary hyperalgesia, innocuous mechanical stimuli elicit pain (allodynia) due to central sensitization of pain pathways. Pruriceptors can also become sensitized in pathophysiological conditions, such as dermatitis. Under chronic itch conditions, low-threshold tactile stimulation can elicit itch (alloknesis), presumably due to central sensitization of itch pathways, although this has not been extensively studied. There is considerable overlap in pain- and itch-signaling pathways and it remains unclear how these sensations are discriminated. Specificity theory states that itch and pain are separate sensations with their own distinct pathways (“labeled lines”). Selectivity theory is similar but incorporates the observation that pruriceptive neurons are also excited by algogenic stimuli that inhibit spinal itch transmission. In contrast, intensity theory states that itch is signaled by low firing rates, and pain by high firing rates, in a common sensory pathway. Finally, the spatial contrast theory proposes that itch is elicited by focal activation of a few nociceptors while activation of more nociceptors over a larger area elicits pain. There is evidence supporting each theory, and it remains to be determined how the nervous system distinguishes between pain and itch.

Caracterización estructural del sistema de ledges y clavos mineralizados del sector Cachinalito, mina El Guanaco, región de Antofagasta, Chile

The high sulfidation epithermal gold deposit El Guanaco is located in the Palaeocene-Lower Eocene metallogenic belt in the Antofagasta Region, northern Chile, 215 km SE of Antofagasta city. The deposit is characterized by a system of sub-parallel ledges made of vuggy silica and quartz enargite veins. In the Cachinalito sector, on the north western side of the ore deposit, the ledges system has a discontinuous linear morphology, with a general ENE-OSO orientation, consisting of many ledges segments that change abruptly in orientation, thickness, length and inclination. Grade analysis distribution, detailed mapping at deposit scale, and identification of individual structures (ledges) shows that one of the key factors in deposit genesis is the structural control. The structural analysis allowed visualizing the different segmentations within a general structure, considering the sizes, horizontal and vertical continuity, degree of connection between ledge segments of different orientations, as well as determining the orientations with greater development of mineralized structures. The distribution of the grades allowed to characterize and identify the ore shoots within the ledges, and to interpret the ascending pathways of the mineralizing fluids by dimensioning and separating the high- and low-grade mineralized sectors. This type of analysis and identification represents an important exploration tool and helps exploration and / or production drilling in this type of deposit.

Circuit organization of the excitatory sensorimotor loop through hand/forelimb S1 and M1

Sensory-guided limb control relies on communication across sensorimotor loops. For active touch with the hand, the longest loop is the transcortical continuation of ascending pathways, particularly the lemnisco-cortical and corticocortical pathways carrying tactile signals via the cuneate nucleus, ventral posterior lateral (VPL) thalamus, and primary somatosensory (S1) and motor (M1) cortices to reach corticospinal neurons and influence descending activity. We characterized excitatory connectivity along this pathway in the mouse. In the lemnisco-cortical leg, disynaptic cuneate→VPL→S1 connections excited mainly layer (L) 4 neurons. In the corticocortical leg, S1→M1 connections from L2/3 and L5A neurons mainly excited downstream L2/3 neurons, which excite corticospinal neurons. The findings provide a detailed new wiring diagram for the hand/forelimb-related transcortical circuit, delineating a basic but complex set of cell-type-specific feedforward excitatory connections that selectively and extensively engage diverse intratelencephalic projection neurons, thereby polysynaptically linking subcortical somatosensory input to cortical motor output to spinal cord.

Breath hold task induces temporal heterogeneity in electroencephalographic regional field power in healthy subjects

While the brainstem is in charge of the automatic control of ventilation, the cortex is involved in the voluntary control of breathing but also receives inputs from the brainstem, which influence the perception of breathing and the arousal state and sleep architecture in conditions of hypoxia/hypercapnia. We evaluated in eleven healthy subjects the effects of breath hold (BH: 30 seconds of apneas and 30 seconds of normal breathing) and BH-related CO2/O2 changes on electroencephalogram (EEG) global field power (GFP) and regional field power (RFP) in 9 different areas (3 rostrocaudal sections -anterior, central, posterior- and 3 sagittal sections -left, middle, right) in the δ and α bands, by cross correlation analysis. No significant differences were observed in GFP and RFP when comparing free breathing (FB) with the BH task. Within the BH task, the shift from apnea to normal ventilation was accompanied by an increase in the δ power and a decrease in the α power. The end-tidal pressure of CO2 (PETCO2) was positively correlated with the δ-band and negatively with the α- band with a positive time shift, while an opposite behaviour was found for the end-tidal pressure of O2 (PETO2). Notably, the time shift between PETCO2/PETO2 signals and cortical activity at RFP was heterogenous and seems to follow a hierarchical activation with the δ-band responding earlier than the α band. Overall, these findings suggest that the effect of BH on the cortex may follow specific ascending pathways from the brainstem and be related to chemoreflex stimulation.

Microflora in the Reproductive Tract of Cattle: A Review

There are microbial communities in and on the bodies of all multicellular organisms, and this microbiota can have a significant impact on the biology of the host. Most studies have focused on the microbiome of the skin, mouth, and gut, whereas relatively little is known about the reproductive microbiome. From the perspective of the bovine reproductive tract, uterine diseases such as metritis and endometritis are traditionally viewed to result only from interactions occurring between the host animal and pathogens originating from either the environment or ascension from the vagina. This outdated opinion has been refuted by recent advanced studies that propose that, in addition to bacteria colonization through the extrinsic and ascending pathways to the vagina, bacteria can also move from the gut to the uterus, which is also associated with reproductive tract disorders. This has led to the concept of the “endogenous route hypothesis”, which has vital inferences for comprehending the etiology of metritis and endometritis. Furthermore, it has opened up the possibility of developing new prophylactic and therapeutic agents as alternatives to antimicrobial agents. In addition, the unveiling of next-generation sequencing technology makes it more convenient to perform detailed sequencing and analysis of data on the cervical, vaginal, and uterine flora and to further study uncultured bacteria in these niches—most importantly, the cervical niche, which previously was thought to have lower bacterial complexity. Research conducted to date has proven that the composition of microflora in a community varies widely between environmental sites, host niches, and health status. Furthermore, it has also been suggested that the occurrence of endometritis in the dairy and beef cattle reproductive tract is neither casual nor indirect but multifactorial. Whether disturbance in the variety of the microflora in the reproductive tract (dysbiosis) has a role in determining the sensitivity to metritis and endometritis is not yet known. This article outlines the current progress in understanding the microflora with regards to the bovine reproductive tract. The compositions of microflora in various niches of the reproductive tract are briefly elucidated. In addition, the functional role of these microflora communities in the reproductive tract is discussed, with particular emphasis on the association of bacterial flora with reproductive disorders and failures. Finally, prophylaxis and therapeutic approaches based on the new comprehension of the effects of antimicrobials, probiotics, and bacteriophages on the composition of the reproductive tract microflora are also considered.

Neuro-Ocular Release: A New Osteopathic Technique For Resolving Somatic Dysfunction

Neuro-ocular release(NOR) is a new osteopathic treatment modality that can be used in conjunction with any indirect osteopathic technique. It is proposed that NOR utilizes the recruitment of the visual system to access the descending pathways, while counterstrain access the ascending pathways, resulting in a resetting of the central and peripheral nervous systems. This resetting allows for dampening of the potentiation of somatic dysfunction (SD). The ascending pathways integrate with many of the vision and ocular reflex pathways influencing the descending response to the peripheral tissues, the location of palpable somatic dysfunction. The authors purport the NOR technique allows for more time efficient and effective treatment by changing the central nervous system entrainment of SD.