Unmyelinated afferents in human skin and their responsiveness to low temperature

In humans, there are different types of cutaneous cold-sensitive afferents responsible for cold sensation and cold pain. Innocuous cold is primarily mediated by a population of slow A delta afferents, based on psychophysical and neurophysiological studies. Noxious cold (usually below 15 degrees C) is mediated, at least in part, by polymodal nociceptors. There is also a population of unmyelinated afferents responsive to innocuous low temperature, some of which also respond to heat, whose sensory function has not been completely defined. A paradoxical hot/burning evoked by cooling is unmasked by A-fibre block, and similar sensations are evoked by applying simultaneous cool and warm stimuli to adjacent skin areas. These unmyelinated fibres activated by innocuous cooling (and heating) may contribute to this hot/burning sensation, along with other thermoregulatory functions.

Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition

Pavlovian fear conditioning, a simple form of associative learning, is thought to involve the induction of associative, NMDA receptor-dependent long-term potentiation (LTP) in the lateral amygdala. Using a combined genetic and electrophysiological approach, we show here that lack of a specific GABA(B) receptor subtype, GABA(B(1a,2)), unmasks a nonassociative, NMDA receptor-independent form of presynaptic LTP at cortico-amygdala afferents. Moreover, the level of presynaptic GABA(B(1a,2)) receptor activation, and hence the balance between associative and nonassociative forms of LTP, can be dynamically modulated by local inhibitory activity. At the behavioral level, genetic loss of GABA(B(1a)) results in a generalization of conditioned fear to nonconditioned stimuli. Our findings indicate that presynaptic inhibition through GABA(B(1a,2)) receptors serves as an activity-dependent constraint on the induction of homosynaptic plasticity, which may be important to prevent the generalization of conditioned fear.

Assessment of the wind-up phenomenon in the equine nociceptive trigeminal system.

Repeated sub-threshold nociceptive electrical stimulation resulting in temporal summation of the limb nociceptive withdrawal reflex is a well-established non-invasive model to investigate the wind-up phenomenon in horses. Due to structural similarities of the trigeminal sensory nucleus to the dorsal horn of the spinal cord, temporal summation should be evoked by repeated transcutaneous electrical stimulation of trigeminal afferents. To evaluate this hypothesis repeated transcutaneous electrical stimulation was applied to the supraorbital and infraorbital nerves of 10 horses. Stimulation intensities varied between 0.5 and 1.3 times the trigemino-cervical reflex threshold defined for single stimulation. Evoked electromyographic activity of the orbicularis oculi, splenius and cleidomastoideus muscles was recorded and the signals analysed in the previously established epochs typical to the early and late component of the blink reflex and to the trigemino-cervical reflex. Behavioural reactions were evaluated with the aid of numerical rating scale. The nociceptive late component and the trigemino-cervical reflex were not elicited by sub-threshold intensity repeated transcutaneous electrical stimulation. Furthermore, the median reflex amplitude for the 10 horses showed a tendency to decline over the stimulation train so temporal summation of afferent trigeminal inputs could not be observed. Therefore, the modulation of trigeminal nociceptive processing attributable to repeated Aδ fibre stimulations seems to differ from spinal processing of similar inputs as it seems to have an inhibitory rather than facilitatory effect. Further evaluation is necessary to highlight the underlying mechanism.

The human vestibular cortex revealed by coordinate-based activation likelihood estimation meta-analysis.

The vestibular system contributes to the control of posture and eye movements and is also involved in various cognitive functions including spatial navigation and memory. These functions are subtended by projections to a vestibular cortex, whose exact location in the human brain is still a matter of debate (Lopez and Blanke, 2011). The vestibular cortex can be defined as the network of all cortical areas receiving inputs from the vestibular system, including areas where vestibular signals influence the processing of other sensory (e.g. somatosensory and visual) and motor signals. Previous neuroimaging studies used caloric vestibular stimulation (CVS), galvanic vestibular stimulation (GVS), and auditory stimulation (clicks and short-tone bursts) to activate the vestibular receptors and localize the vestibular cortex. However, these three methods differ regarding the receptors stimulated (otoliths, semicircular canals) and the concurrent activation of the tactile, thermal, nociceptive and auditory systems. To evaluate the convergence between these methods and provide a statistical analysis of the localization of the human vestibular cortex, we performed an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies using CVS, GVS, and auditory stimuli. We analyzed a total of 352 activation foci reported in 16 studies carried out in a total of 192 healthy participants. The results reveal that the main regions activated by CVS, GVS, or auditory stimuli were located in the Sylvian fissure, insula, retroinsular cortex, fronto-parietal operculum, superior temporal gyrus, and cingulate cortex. Conjunction analysis indicated that regions showing convergence between two stimulation methods were located in the median (short gyrus III) and posterior (long gyrus IV) insula, parietal operculum and retroinsular cortex (Ri). The only area of convergence between all three methods of stimulation was located in Ri. The data indicate that Ri, parietal operculum and posterior insula are vestibular regions where afferents converge from otoliths and semicircular canals, and may thus be involved in the processing of signals informing about body rotations, translations and tilts. Results from the meta-analysis are in agreement with electrophysiological recordings in monkeys showing main vestibular projections in the transitional zone between Ri, the insular granular field (Ig), and SII.

Balancing the mind: vestibular induced facilitation of egocentric mental transformations

The body schema is a key component in accomplishing egocentric mental transformations, which rely on bodily reference frames. These reference frames are based on a plurality of different cognitive and sensory cues among which the vestibular system plays a prominent role. We investigated whether a bottom-up influence of vestibular stimulation modulates the ability to perform egocentric mental transformations. Participants were significantly faster to make correct spatial judgments during vestibular stimulation as compared to sham stimulation. Interestingly, no such effects were found for mental transformation of hand stimuli or during mental transformations of letters, thus showing a selective influence of vestibular stimulation on the rotation of whole-body reference frames. Furthermore, we found an interaction with the angle of rotation and vestibular stimulation demonstrating an increase in facilitation during mental body rotations in a direction congruent with rightward vestibular afferents. We propose that facilitation reflects a convergence in shared brain areas that process bottom-up vestibular signals and top-down imagined whole-body rotations, including the precuneus and tempero-parietal junction. Ultimately, our results show that vestibular information can influence higher-order cognitive processes, such as the body schema and mental imagery.

Neural correlate of spatial presence in an arousing and noninteractive virtual reality: an EEG and psychophysiology study

Using electroencephalography (EEG), psychophysiology, and psychometric measures, this is the first study which investigated the neurophysiological underpinnings of spatial presence. Spatial presence is considered a sense of being physically situated within a spatial environment portrayed by a medium (e.g., television, virtual reality). Twelve healthy children and 11 healthy adolescents were watching different virtual roller coaster scenarios. During a control session, the roller coaster cab drove through a horizontal roundabout track. The following realistic roller coaster rides consisted of spectacular ups, downs, and loops. Low-resolution brain electromagnetic tomography (LORETA) and event-related desynchronization (ERD) were used to analyze the EEG data. As expected, we found that, compared to the control condition, experiencing a virtual roller coaster ride evoked in both groups strong SP experiences, increased electrodermal reactions, and activations in parietal brain areas known to be involved in spatial navigation. In addition, brain areas that receive homeostatic afferents from somatic and visceral sensations of the body were strongly activated. Most interesting, children (as compared to adolescents) reported higher spatial presence experiences and demonstrated a different frontal activation pattern. While adolescents showed increased activation in prefrontal areas known to be involved in the control of executive functions, children demonstrated a decreased activity in these brain regions. Interestingly, recent neuroanatomical and neurophysiological studies have shown that the frontal brain continues to develop to adult status well into adolescence. Thus, the result of our study implies that the increased spatial presence experience in children may result from the not fully developed control functions of the frontal cortex.

The pre- and post-somatic segments of the human type I spiral ganglion neurons--structural and functional considerations related to cochlear implantation.

Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-β2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-β2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-β2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.

Autonomic angiotensinergic fibres in the human heart with an efferent sympathetic cophenotype

AIM The autonomic innervation of the heart consists of sympathetic and parasympathetic nerve fibres, and fibres of the intrinsic ganglionated plexus with noradrenaline and acytylcholine as principal neurotransmitters. The fibres co-release neuropeptides to modulate intracardiac neurotransmission by specific presynaptic and postsynaptic receptors. The coexpression of angiotensin II in sympathetic fibres of the human heart and its role are not known so far. METHODS Autopsy specimens of human hearts were studied (n=3; ventricles). Using immunocytological methods, cryostat sections were stained by a murine monoclonal antibody (4B3) directed against angiotensin II and co-stained by polyclonal antibodies against tyrosine hydroxylase, a catecholaminergic marker. Visualisation of the antibodies was by confocal light microscopy or laser scanning microscopy. RESULTS Angiotensin II-positive autonomic fibres with and without a catecholaminergic cophenotype (hydroxylase-positive) were found in all parts of the human ventricles. In the epicardium, the fibres were grouped in larger bundles of up to 100 and more fibres. They followed the preformed anatomic septa and epicardial vessels towards the myocardium and endocardium where the bundles dissolved and the individual fibres spread between myocytes and within the endocardium. Generally, angiotensinergic fibres showed no synaptic enlargements or only a few if they were also catecholaminergic. The exclusively catechalominergic fibres were characterised by multiple beaded synapses. CONCLUSION The autonomic innervation of the human heart contains angiotensinergic fibres with a sympathetic efferent phenotype and exclusively angiotensinergic fibers representing probably afferents. Angiotensinergic neurotransmission may modulate intracardiac sympathetic and parasympathetic activity and thereby influence cardiac and circulatory function.