Principal Sensory Nucleus Research Articles

Mapping of mitochondrial ferritin in the brainstem of Macaca fascicularis

Mitochondrial ferritin (FtMt), a recently-studied iron storage protein, which we suspect is an important defense against oxidative stress in neurons and elsewhere. The 242-amino acid FtMt precursor protein is cleaved to mature protein (of molecular weight about 22-kDa) in the mitochondrial matrix. Compared with the ubiquitously expressed traditional ferritin (H-ferritin and L-ferritin), FtMt has been found in fewer locations including the testis, heart and brain. Previous studies have reported that the expression of FtMt in mouse and human brain is predominantly localized to neurons and partly to glial cells, and FtMt exerts protective effects on neurons by maintaining normal function and regulates apoptosis in Alzheimer’s disease and Parkinson’s disease. To find out the function of FtMt in neurodegenerative disease, we had a novel antibody made against human FtMt and characterized it via Western blot analysis, immunoabsorption testing, and double immunofluorescence histochemistry. Then we used this new FtMt antibody to map the distribution of FtMt in the monkey brainstem. We demonstrated widespread distribution of FtMt immunoreactivity throughout the monkey brainstem, with variable staining intensity. FtMt immunoreactivity was observed in the extrapyramidal system, sensory trigeminal nerve nuclei, some motor nuclei including ambiguous nucleus, dorsal motor nucleus of the vagus and hypoglossal nucleus, and some dorsal column nuclei such as the gracile nucleus and cuneate nucleus. In addition, double immunohistochemical stainings confirmed that FtMt immunoreactivity was co-localized with catecholaminergic neurons in the locus coeruleus (63.64%), substantia nigra pars compacta (69.18%), and ventral tegmental area (56.89%). The distribution of FtMt which we found in the brainstem implies possible involvement of FtMt in several physiological mechanisms, especially in the catecholaminergic neurons, and the possibility of significant involvement in neurodegenerative disease.

Revisiting the supratrigeminal nucleus in the rat

The supratrigeminal nucleus (Vsup), originally proposed as a premotoneuron pool in the trigeminal reflex arc, is a key structure of jaw movement control. Surprisingly, however, the location of the rat Vsup has not precisely been defined. In light of our previous cat studies, we made two hypotheses regarding the rat Vsup: (1) the Vsup is cytoarchitectonically distinguishable from its surrounding structures; (2) the Vsup receives central axon terminals of the trigeminal mesencephalic nucleus (Vmes) neurons which are primary afferents innervating muscle spindles of jaw-closing muscles and periodontal ligaments around the teeth. To test the first hypothesis, we examined the cytoarchitecture of the rat Vsup. The Vsup was identified as an area medially adjacent to the dorsomedial part of trigeminal principal sensory nucleus (Vp), and extended from the level just rostral to the caudal two-thirds of the trigeminal motor nucleus (Vmo) to the level approximately 150μm caudal to the Vmo. Our rat Vsup was much smaller and its location was considerably different in comparison to the Vsup reported previously. To evaluate the second hypothesis, we tested the distribution patterns of Vmes primary afferent terminals in the cytoarchitectonically identified Vsup. After transganglionic tracer applications to the masseter, deep temporal, and medial pterygoid nerves, a large number of axon terminals were observed in all parts of Vsup (especially in its medial part). After applications to the inferior alveolar, infraorbital, and lingual nerves, a small number of axon terminals were labeled in the caudolateral Vsup. The Vsup could also be identified electrophysiologically. After electrical stimulation of the masseter nerve, evoked potentials with slow negative component were isolated only in the Vsup. The present findings suggest that the rat Vsup can be cytoarchitectonically and electrophysiologically identified, receives somatotopic termination of the trigeminal primary afferents, and principally receives strong termination of the spindle Vmes primary afferents.

Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal).

The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms.

SCN2B in the Rat Trigeminal Ganglion and Trigeminal Sensory Nuclei.

The beta-2 subunit of the mammalian brain voltage-gated sodium channel (SCN2B) was examined in the rat trigeminal ganglion (TG) and trigeminal sensory nuclei. In the TG, 42.6% of sensory neurons were immunoreactive (IR) for SCN2B. These neurons had various cell body sizes. In facial skins and oral mucosae, corpuscular nerve endings contained SCN2B-immunoreactivity. SCN2B-IR nerve fibers formed nerve plexuses beneath taste buds in the tongue and incisive papilla. However, SCN2B-IR free nerve endings were rare in cutaneous and mucosal epithelia. Tooth pulps, muscle spindles and major salivary glands were also innervated by SCN2B-IR nerve fibers. A double immunofluorescence method revealed that about 40% of SCN2B-IR neurons exhibited calcitonin gene-related peptide (CGRP)-immunoreactivity. However, distributions of SCN2B- and CGRP-IR nerve fibers were mostly different in facial, oral and cranial structures. By retrograde tracing method, 60.4 and 85.3% of TG neurons innervating the facial skin and tooth pulp, respectively, showed SCN2B-immunoreactivity. CGRP-immunoreactivity was co-localized by about 40% of SCN2B-IR cutaneous and tooth pulp TG neurons. In trigeminal sensory nuclei of the brainstem, SCN2B-IR neuronal cell bodies were common in deep laminae of the subnucleus caudalis, and the subnuclei interpolaris and oralis. In the mesencephalic trigeminal tract nucleus, primary sensory neurons also exhibited SCN2B-immunoreactivity. In other regions of trigeminal sensory nuclei, SCN2B-IR cells were very infrequent. SCN2B-IR neuropil was detected in deep laminae of the subnucleus caudalis as well as in the subnuclei interpolaris, oralis and principalis. These findings suggest that SCN2B is expressed by various types of sensory neurons in the TG. There appears to be SCN2B-containing pathway in the TG and trigeminal sensory nuclei.

Facialis vírusinokuláció fertőzi a vestibularis és cochlearis agyidegmagokat

Background and purpose – There is growing evidence for the viral origin of the Bell’s facial palsy, vestibular neuritis and sudden sensorineural hearing loss, however their exact pathophysiology is still unknown. We investigated the possibility of brainstem infections following peripheral viral inoculations in rats. Methods – Pseudorabies virus, a commonly used neurotropic viral retrograde tracer was injected into the nasolabial region of rats. Five and 6 days after injections, infected brainstem nuclei were demonstrated by immunohistochemical techniques. Results – Infected neurons were found in the motor facial, the medial vestibular, and the sensory trigeminal nuclei, as well as in the medial nucleus of the trapezoid body. Conclusion – Pseudorabies virus infects auditory and vestibular sensory neurons in the brainstem through facial inoculation. The possible routes of infections: 1. trans-synaptic spread constituted by facio-vestibular anastomoses: primarily infected motor facial neuron infects neurons in the medial vestibular nucleus, 2. via trigeminal sensory nerves: the sensory trigeminal complex innervated by GABAergic medial vestibular neurons, and 3. one bisynaptical route: infected facial motoneurons may receive indirect input from the medial vestibular nucleus and the trapezoid body via connecting neurons in the sensory trigeminal complex. We may assume that latent infections of these areas may precede the infections of the peripheral organs and the reactivation of the virus exerts the symptoms.

C1-O-05Central Connectivity and Distribution of Transient Receptor Potential Melastatin 8 (TRPM8)-expressing Axons in the Brain stem and Dental pulp

Elucidation of synaptic connectivities of the specific primary sensory afferents, involved neurotransmitters and receptors may help understand how the specific sensation conveyed via particular sensory afferents is processed at the 1st relay nucleus. Transient receptor potential melastatin 8 (TRPM8) mediates detection of noxious cold and innocuous cool, and is expressed in the primary sensory neurons. In this presentation, we will talk about our recent findings on expression and central connectivities of TRPM8-positive (+) axons in the trigeminal sensory nuclei (TSN) and their coexpression with vesicular glutamate transporters (VGLUTs) in the dental pulp. TRPM8 was expressed in unmyelinated C fibers (76%) and small myelinated Αδ fibers (24%). TRPM8+ axons were observed in all TSN, but at different densities in the dorsal and ventral areas of the rostral TSN, suggesting TRPM8-mediated cold from face and intraoral area is processed in different level of TSN. TRPM8+ boutons, compared to boutons from the same class of fiber types, showed unique synaptic connectivity; simple synapses with one or two dendrites and sparse axoaxonic contacts. In the dental pulp, TRPM8+ axons were densely distributed in the peripheral pulp, coexpressed VGLUT2, but not VGLUT1, and which was upregulated following pulpal inflammation. These findings suggest that TRPM8 -mediated cold is processed in a unique manner and differently in the TSN and also suggest existence of VLGUT2-mediated glutamate signaling in TRPM8+ axons that may be underlying mechanism for acute cold pain and cold hypersensitivity following inflammation.

Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus

Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1h at 1bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans.The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume.These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing.

Hoxa2 Selects Barrelette Neuron Identity and Connectivity in the Mouse Somatosensory Brainstem.

Mouse whiskers are somatotopically mapped in brainstem trigeminal nuclei as neuronal modules known as barrelettes. Whisker-related afferents form barrelettes in ventral principal sensory (vPrV) nucleus, whereas mandibular input targets dorsal PrV (dPrV). How barrelette neuron identity and circuitry is established is poorly understood. We found that ectopic Hoxa2 expression in dPrV neurons is sufficient to attract whisker-related afferents, induce asymmetrical dendrite arbors, and allow ectopic barrelette map formation. Moreover, the thalamic area forming whisker-related barreloids is prenatally targeted by both vPrV and dPrV axons followed by perinatal large-scale pruning of dPrV axons and refinement of vPrV barrelette input. Ectopic Hoxa2 expression allows topographically directed targeting and refinement of dPrV axons with vPrV axons into a single whisker-related barreloid map. Thus, a single HOX transcription factor is sufficient to switch dPrV into a vPrV barrelette neuron program and coordinate input-output topographic connectivity of a dermatome-specific circuit module.

Corticofugal projection patterns of whisker sensorimotor cortex to the sensory trigeminal nuclei.

The primary (S1) and secondary (S2) somatosensory cortices project to several trigeminal sensory nuclei. One putative function of these corticofugal projections is the gating of sensory transmission through the trigeminal principal nucleus (Pr5), and some have proposed that S1 and S2 project differentially to the spinal trigeminal subnuclei, which have inhibitory circuits that could inhibit or disinhibit the output projections of Pr5. Very little, however, is known about the origin of sensorimotor corticofugal projections and their patterns of termination in the various trigeminal nuclei. We addressed this issue by injecting anterograde tracers in S1, S2 and primary motor (M1) cortices, and quantitatively characterizing the distribution of labeled terminals within the entire rostro-caudal chain of trigeminal sub-nuclei. We confirmed our anterograde tracing results by injecting retrograde tracers at various rostro-caudal levels within the trigeminal sensory nuclei to determine the position of retrogradely labeled cortical cells with respect to S1 barrel cortex. Our results demonstrate that S1 and S2 projections terminate in largely overlapping regions but show some significant differences. Whereas S1 projection terminals tend to cluster within the principal trigeminal (Pr5), caudal spinal trigeminal interpolaris (Sp5ic), and the dorsal spinal trigeminal caudalis (Sp5c), S2 projection terminals are distributed in a continuum across all trigeminal nuclei. Contrary to the view that sensory gating could be mediated by differential activation of inhibitory interconnections between the spinal trigeminal subnuclei, we observed that projections from S1 and S2 are largely overlapping in these subnuclei despite the differences noted earlier.

Neonatal low-protein diet reduces the masticatory efficiency in rats.

Little is known about the effects of undernutrition on the specific muscles and neuronal circuits involved in mastication. The aim of this study was to document the effects of neonatal low-protein diet on masticatory efficiency. Newborn rats whose mothers were fed 17% (nourished (N), n 60) or 8% (undernourished (U), n 56) protein were compared. Their weight was monitored and their masticatory jaw movements were video-recorded. Whole-cell patch-clamp recordings were performed in brainstem slice preparations to investigate the intrinsic membrane properties and N-methyl-d-aspartate-induced bursting characteristics of the rhythmogenic neurons (N, n 43; U, n 39) within the trigeminal main sensory nucleus (NVsnpr). Morphometric analysis (N, n 4; U, n 5) were conducted on masseteric muscles serial cross-sections. Our results showed that undernourished animals had lower numbers of masticatory sequences (P=0·049) and cycles (P=0·045) and slower chewing frequencies (P=0·004) (N, n 32; U, n 28). Undernutrition reduced body weight but had little effect on many basic NVsnpr neuronal electrophysiological parameters. It did, however, affect sag potentials (P<0·001) and rebound firing (P=0·005) that influence firing pattern. Undernutrition delayed the appearance of bursting and reduced the propensity to burst (P=0·002), as well as the bursting frequency (P=0·032). Undernourished animals showed increased and reduced proportions of fibre type IIA (P<0·0001) and IIB (P<0·0001), respectively. In addition, their fibre areas (IIA, P<0·001; IIB, P<0·001) and perimeters (IIA, P<0·001; IIB, P<0·001) were smaller. The changes observed at the behavioural, neuronal and muscular levels suggest that undernutrition reduces chewing efficiency by slowing, weakening and delaying maturation of the masticatory muscles and the associated neuronal circuitry.

Timing of mammalian peripheral trigeminal system development relative to body size: A comparison of metatherians with rodents and monotremes

Specializations of the trigeminal sensory system are present in all three infraclasses of mammals (metatheria, eutheria, prototheria or monotremata). The trigeminal sensory system has been suggested as a critically important modality for sampling the path to the pouch and detecting the nipple or milk patch, but the degree to which that system may be required to function at birth varies significantly. Archived sections of the snout and brainstem of embryonic and postnatal mammals were used to test the relationship between structural maturity of the two ends of the trigeminal nerve pathway and the body size of mammalian young in metatherians, rodents and monotremes. A system for staging different levels of structural maturity of the vibrissae and trigeminal sensory was applied to embryos, pouch young and hatchlings and correlated with body length. Dasyurids are born at the most immature state with respect to vibrissal and trigeminal sensory nucleus development of any available metatherian, but these components of the trigeminal system are also developmentally advanced relative to body size when dasyurids are compared to other metatherians. Vibrissal and trigeminal sensory nucleus development is at a similar stage of development at birth and for a given body size in non-dasyurid metatherians; and trigeminal sensory nucleus development in monotremes is at a similar stage at birth to metatherians. Rodents reach a far more advanced stage of vibrissal and trigeminal sensory nucleus development at birth than do metatherians, and in the case of the mouse have a more developmentally advanced trigeminal system than all available metatherians at any given body length. Precocious development of the trigeminal sensory pathway relative to body size is evident in dasyurids, as might be expected given the small birth size of those metatherians. Nevertheless, the trigeminal sensory system in metatherians in general is not precocious relative to body size when these species are considered alongside the pace of trigeminal somatosensory development in rodents.

At the centre of neuronal, synaptic and axonal pathology in murine prion disease: degeneration of neuroanatomically linked thalamic and brainstem nuclei.

AimsThe processes by which neurons degenerate in chronic neurodegenerative diseases remain unclear. Synaptic loss and axonal pathology frequently precede neuronal loss and protein aggregation demonstrably spreads along neuroanatomical pathways in many neurodegenerative diseases. The spread of neuronal pathology is less studied.MethodsWe previously demonstrated severe neurodegeneration in the posterior thalamus of multiple prion disease strains. Here we used the ME7 model of prion disease to examine the nature of this degeneration in the posterior thalamus and the major brainstem projections into this region.ResultsWe objectively quantified neurological decline between 16 and 18 weeks post‐inoculation and observed thalamic subregion‐selective neuronal, synaptic and axonal pathology while demonstrating relatively uniform protease‐resistant prion protein (PrP) aggregation and microgliosis across the posterior thalamus. Novel amyloid precursor protein (APP) pathology was particularly prominent in the thalamic posterior (PO) and ventroposterior lateral (VPL) nuclei. The brainstem nuclei forming the major projections to these thalamic nuclei were examined. Massive neuronal loss in the PO was not matched by significant neuronal loss in the interpolaris (Sp5I), while massive synaptic loss in the ventral posteromedial nucleus (VPM) did correspond with significant neuronal loss in the principal trigeminal nucleus. Likewise, significant VPL synaptic loss was matched by significant neuronal loss in the gracile and cuneate nuclei.ConclusionThese findings demonstrate significant spread of neuronal pathology from the thalamus to the brainstem in prion disease. The divergent neuropathological features in adjacent neuronal populations demonstrates that there are discrete pathways to neurodegeneration in different neuronal populations.

Anatomical organization of descending cortical projections orchestrating the patterns of cortically induced rhythmical jaw muscle activity in guinea pigs

Repetitive electrical microstimulation to the cortical masticatory area (CMA) evokes distinct patterns of rhythmical jaw muscle activities (RJMAs) in animals. This study aimed to investigate the characteristics of the descending projections from the CMA, associated with distinct patterns of RJMAs, to the thalamus, midbrain, pons and medulla in guinea pigs. RJMAs with continuous masseter and digastric bursts (CB-RJMAs) and stimulus-locked digastric sub-bursts (SLB-RJMAs) were induced from the anterior and posterior areas of the rostral region of the lateral agranular cortex, and chewing-like RJMAs from the rostral region of the granular cortex. Anterograde tracer, biotinylated dextran amine, was injected into the three cortical areas. The cortical area inducing CB-RJMAs had strong ipsilateral projections to the motor thalamus, red nucleus, midbrain reticular formation, superior colliculus, parabrachial nucleus, and supratrigeminal region, and contralateral projections mainly to the lateral reticular formation around the trigeminal motor nucleus (Vmo). The cortical area inducing SLB-RJMAs had moderate projections to the motor thalamus and lateral reticular formation around the Vmo, but few projections to the midbrain nuclei. The cortical area inducing chewing-like RJMAs had strong projections to the ipsilateral sensory thalamus and contralateral trigeminal sensory nuclei, and moderate projections to the lateral reticular formation. The three cortical areas consistently had few projections to the ventromedial reticular formation. The present study demonstrates that multiple direct and indirect descending projections from the CMA onto the premotor systems connecting the trigeminal motoneurons represent the neuroanatomical repertoires for generating RJMAs during the distinct phases of natural ingestive behavior.

Subcortical barrelette-like and barreloid-like structures in the prosimian galago (Otolemur garnetti)

Galagos are prosimian primates that resemble ancestral primates more than most other extant primates. As in many other mammals, the facial vibrissae of galagos are distributed across the upper and lower jaws and above the eye. In rats and mice, the mystacial macrovibrissae are represented throughout the ascending trigeminal pathways as arrays of cytoarchitecturally distinct modules, with each module having a nearly one-to-one relationship with a specific facial whisker. The macrovibrissal representations are termed barrelettes in the trigeminal somatosensory brainstem, barreloids in the ventroposterior medial subnucleus of the thalamus, and barrels in primary somatosensory cortex. Despite the presence of facial whiskers in all nonhuman primates, barrel-like structures have not been reported in primates. By staining for cytochrome oxidase, Nissl, and vesicular glutamate transporter proteins, we show a distinct array of barrelette-like and barreloid-like modules in the principal sensory nucleus, the spinal trigeminal nucleus, and the ventroposterior medial subnucleus of the galago, Otolemur garnetti. Labeled terminals of primary sensory neurons in the brainstem and cell bodies of thalamocortically projecting neurons demonstrate that barrelette-like and barreloid-like modules are located in areas of these somatosensory nuclei that are topographically consistent with their role in facial touch. Serendipitously, the plane of section that best displays the barreloid-like modules reveals a remarkably distinct homunculus-like patterning which, we believe, is one of the clearest somatotopic maps of an entire body surface yet found.

Trigeminal‐hypoglossal silent period: A pontomedullary brainstem reflex

Animal studies have shown inhibitory connections between the sensory trigeminal nucleus and hypoglossal nucleus. I investigated whether these inhibitory projections are present in humans. I examined 18 healthy subjects, 2 patients with brainstem stroke, and 5 patients with multiple sclerosis using a specially designed oral stimulation and recording device. In 16 of 18 subjects, a bilateral suppression period of tongue muscle activity after unilateral electrical stimulation of the mucosal V2 afferents was observed. The silent period started at 31.1 (SD 4.7) ms (ipsilateral) and 32.0 (SD 4.9) ms (contralateral). The mean duration of the silent period was 31.4 (SD 10.2) ms (ispilateral) and 32.5 (SD 9.8) ms (contralateral). Patients with dorsolateral pontomedullary lesions had ipsilateral absence of the silent period. This study confirms the existence of a bilateral trigeminal-hypoglossal silent period in humans.

Phylogenic Oto-stomatognathic Connection of the Mammalian Jaw: A Novel Hypothesis for Tensor Tympani Muscle and TMD-related Otologic Symptoms

Otologic complaints, including otalgia, tinnitus, vertigo, and hearing loss, are known to be related to temporomandibular disorders (TMDs). There have been several hypotheses regarding the clinical correlation between otologic complaints and TMDs, based on clinical phenomena with corresponding symptoms, the close neurological relationship between otic and masticatory structures, and anatomical features of the tympanic cavity and jaw joint. Function of the tensor tympani muscle seems to be crucial to understanding TMD-related otologic symptoms. The tensor tympani inserts into the handle of the malleus and it modulates sound transduction in situations of excessive noise. This muscle is innervated by the trigeminal nerve, like the masticatory muscles. Voluntary eardrum movement by pathological tensor tympani contraction results in various otologic symptoms. Thus, co-contraction of the tensor tympani with the masticatory muscle could be a possible cause of TMD-related otologic symptoms. The tensor tympani is rather unrelated to the acoustic reflex, in which the stapedius is strongly involved. The tensor tympani seem to be controlled by proprioceptive information from the trigeminal sensory nucleus. The peripheral innervation pattern of the tensor tympani and masticatory muscles is also supposed to be interconnected. The middle ear structure, including the malleus, incus, and tensor tympani, of mammals had been adapted for acoustic function and lacks the masticatory role seen in non-mammalian jawed vertebrates. The tensor tympani in non-mammals is one of the masticatory muscles and plays a role in the modulation of sound transduction and mastication. After the functional differentiation of the mammalian middle ear, the nervous connection of the tensor tympani with other masticatory apparatus still remains. Through this oto-stomatognathic vestige, the tensor tympani seems to contract unnecessarily in some pathological conditions of the TMD in which the masticatory muscles contract excessively. We hypothesized that the phylogenic relationship between the tensor tympani and masticatory apparatus is a significant and logical reason for TMD-related otologic complaints.

Facial whisker pattern is not sufficient to instruct a whisker-related topographic map in the mouse somatosensory brainstem.

Facial somatosensory input is relayed by trigeminal ganglion (TG) neurons and serially wired to brainstem, thalamus and cortex. Spatially ordered sets of target neurons generate central topographic maps reproducing the spatial arrangement of peripheral facial receptors. Facial pattern provides a necessary template for map formation, but may be insufficient to impose a brain somatotopic pattern. In mice, lower jaw sensory information is relayed by the trigeminal nerve mandibular branch, whose axons target the brainstem dorsal principal sensory trigeminal nucleus (dPrV). Input from mystacial whiskers is relayed by the maxillary branch and forms a topographic representation of rows and whiskers in the ventral PrV (vPrV). To investigate peripheral organisation in imposing a brain topographic pattern, we analysed Edn1(-/-) mice, which present ectopic whisker rows on the lower jaw. We found that these whiskers were innervated by mandibular TG neurons which initially targeted dPrV. Unlike maxillary TG neurons, the ectopic whisker-innervating mandibular neuron cell bodies and pre-target central axons did not segregate into a row-specific pattern nor target the dPrV with a topographic pattern. Following periphery-driven molecular repatterning to a maxillary-like identity, mandibular neurons partially redirected their central projections from dPrV to vPrV. Thus, while able to induce maxillary-like molecular features resulting in vPrV final targeting, a spatially ordered lower jaw ectopic whisker pattern is insufficient to impose row-specific pre-target organisation of the central mandibular tract or a whisker-related matching pattern of afferents in dPrV. These results provide novel insights into periphery-dependent versus periphery-independent mechanisms of trigeminal ganglion and brainstem patterning in matching whisker topography.

Severe headache with eye involvement from herpes zoster ophthalmicus, trigeminal tract, and brainstem nuclei.

A 43-year-old female presented with severe sharp stabbing right-sided periorbital and retroorbital area headache, dull-aching unilateral jaw pain, eyelid swelling, ptosis, and tearing of the right eye but no rash. The pain episodes lasted five minutes to one hour and occurred 10–15 times per day with unremitting milder pain between the attacks. She later developed an erythematous maculopapular rash over the right forehead and therefore was treated with antivirals. MRI performed one month after the onset revealed small hypersignal-T2 in the right dorsolateral mid-pons and from the right dorsolateral aspect of the pontomedullary region to the right dorsolateral aspect of the upper cervical cord, along the course of the principal sensory nucleus and spinal nucleus of the right trigeminal nerve. No definite contrast enhancement of the right brain stem/upper cervical cord was seen. Orbital imaging showed no abnormality of bilateral optic nerves/chiasm, extraocular muscles, and globes. Slight enhancement of the right V1, V2, and the cisterna right trigeminal nerve was detected. Our findings support the hypothesis of direct involvement by virus theory, reflecting rostral viral transmission along the gasserian ganglion to the trigeminal nuclei at brainstem and caudal spreading along the descending tract of CN V.

More a finger than a nose: the trigeminal motor and sensory innervation of the Schnauzenorgan in the elephant-nose fish Gnathonemus petersii.

The weakly electric fish Gnathonemus petersii uses its electric sense to actively probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is rich in electroreceptors. Physical measurements have demonstrated the importance of the position of the Schnauzenorgan in funneling the fish's self-generated electric field. The present study focuses on the trigeminal motor pathway that controls Schnauzenorgan movement and on its trigeminal sensory innervation and central representation. The nerves entering the Schnauzenorgan are very large and contain both motor and sensory trigeminal components as well as an electrosensory pathway. With the use of neurotracer techniques, labeled Schnauzenorgan motoneurons were found throughout the ventral main body of the trigeminal motor nucleus but not among the population of larger motoneurons in its rostrodorsal region. The Schnauzenorgan receives no motor or sensory innervation from the facial nerve. There are many anastomoses between the peripheral electrosensory and trigeminal nerves, but these senses remain separate in the sensory ganglia and in their first central relays. Schnauzenorgan trigeminal primary afferent projections extend throughout the descending trigeminal sensory nuclei, and a few fibers enter the facial lobe. Although no labeled neurons could be identified in the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic, possibly proprioceptive, pathway. In this first step toward understanding multimodal central representation of the Schnauzenorgan, no direct interconnections were found between the trigeminal sensory and electromotor command system, or the electrosensory and trigeminal motor command. The pathways linking perception to action remain to be studied.

Tactile response adaptation to whisker stimulation in the lemniscal somatosensory pathway of rats

Response adaptation is associated with attenuation of neural responses as the result of different mechanisms. However, the main function of adaptation may be to enhance the flow of relevant information transmission in sensory pathways. To study tactile response adaptation in the somatosensory pathway, unit recordings were performed in the principal trigeminal nucleus, ventro postero-medial thalamic nucleus and barrel cortex by means of tungsten microelectrodes in urethane anesthetized rats. Tactile stimuli consisted in 20ms duration whisker deflections at different frequencies (0.5–10Hz). Presumably pyramidal cortical neurons showed response adaptation at frequencies >2Hz while putative inhibitory cortical neurons did not show response adaptation at 0.5, 5 or 10Hz. Inhibitory activity was increased by muscimol application into the cortex (8mM, 0.1µl); in this condition cortical adaptation was not affected, suggesting that adaptation was not due to an increase of inhibitory mechanisms. Adaptation was also observed in subcortical structures although the response attenuation was lesser than in the barrel cortex. Adaptation remained in subcortical structures after reversible cortical inactivation by cooling the barrel cortex. Acetylcholine application (10μM; 0.1μl) into the barrel cortex reduced response adaptation through the activation of muscarinic receptors because the effect was blocked by intraperitoneal injection of atropine (1mg/kg), suggesting that adaptation may change according to the cortical Ach level. Results indicate that response adaptation increases along the somatosensory pathway probably to alter the sensitivity of neurons in order to encode sensory stimuli more efficiently and to enhance the detectability of rare stimuli.