Dentate gyrus and olfactory bulb responses to olfactory and noxious stimulation in urethane anaesthetized rats

Recent research has shown that olfactory stimuli such as toluene vapor, but not visual, auditory, tactile or gustatory stimuli, elicit a burst of fast waves (15–30 Hz) in the hilus of the dentate gyrus in waking rats. In urethane-anaesthetized rats, toluene odors elicit similar fast waves. The present study shows that noxious stimulation (tail clamp) produces a blockade of spontaneous slow waves (1–12 Hz) in the hilus of the dentate gyrus but does not increase fast wave activity in urethane-anaesthetized rats. This slow wave blockade, which resembles neocortical activation, is independent of olfaction since it is not affected by tracheotomy. In contrast, tracheotomy abolishes the fast wave response to toluene presentation to the snout unless the toluene vapor is drawn into the nasal passages by suction at the rostral end of the servered trachea. Both the toluene odor-induced fast wave and the tail clamp-induced activation responses are abolished by scopolamine hydrobromide (5.0 mg/kg, i.p.) but not by scopolamine methyl bromide (5.0 mg/kg, i.p.) which does not cross the blood-brain barrier. However, evoked potentials elicited in the dentate hilus by single pulse stimulation of the olfactory bulb are not blocked by scopolamine in urethane-anaesthetized rats. The results suggest that several different types of electrical activity in the hippocampal formation are mediated by cholinergic inputs and that the dentate gyrus plays a role in olfaction.     

Pupillary responses and blink reflex in myotonic dystrophy

Research Paper We have studied pupillary responses to parasympathetic and sympathomimetic agents, pupillary cycle time and the electrophysiology of the blink reflex in 18 patients with myotonic dystrophy. The response of the iris to dilute pilocarpine and phenylephrine did not indicate pharmacologic supersensitivity. Pupillary cycle time was prolonged in nine of the 18 patients. Ipsilateral R₁ blink reflex latencies were normal in all cases, and bilateral R₂ were normal in 16 of the 18 patients. These results do not support either autonomic or brainstem dysfunction in the majority of patients with myotonic dystrophy. In 50% of the patients the results are compatible with smooth muscle involvement of the iris.     

Trigeminal system in Parkinson's disease: A potential avenue to detect Parkinson-specific olfactory dysfunction

BackgroundOlfactory dysfunction (OD) is very frequent in Parkinson's disease (PD) and observed years before diagnosis. The trigeminal system, a chemosensory system allowing for the perception of spiciness, freshness, etc., is intimately connected to the olfactory system and although usually reduced in OD the trigeminal system is not well characterized in PD. We hypothesize that measuring trigeminal sensitivity potentially allows to discriminate between OD due to PD and OD due to other causes to potentially help the development of an early diagnostic tool.ObjectiveTo evaluate olfactory and trigeminal sensitivity and perception in PD patients and compare them to participants with non-parkinsonian OD (NPOD) and to healthy controls.MethodsWe assessed olfactory function using “Sniffin’ Sticks test” and trigeminal function with the localization task in 28 PD patients, 27 healthy controls and 21 patients with OD unrelated to PD.ResultsPD patients exhibited significantly higher trigeminal sensitivity than NPOD patients (p = 0.002) and performed similar to healthy controls. In contrast, PD and NPOD patients had both similar olfactory scores, significantly below healthy controls.ConclusionThe trigeminal system seems not to be impaired in PD patients even in the presence of OD. Measuring trigeminal sensitivity may therefore allow to differentiate PD-related OD from other forms of OD.     

In vivo visualization of olfactory pathophysiology induced by intranasal cadmium instillation in mice

Intranasal exposure to cadmium has been related to olfactory dysfunction in humans and to nasal epithelial damage and altered odorant-guided behavior in rodent models. The pathophysiology underlying these deficits has not been fully elucidated. Here we use optical imaging techniques to visualize odorant-evoked neurotransmitter release from the olfactory nerve into the brain's olfactory bulbs in vivo in mice. Intranasal cadmium chloride instillations reduced this sensory activity by up to 91% in a dose-dependent manner. In the olfactory bulbs, afferents from the olfactory epithelium could be quantified by their expression of a genetically encoded fluorescent marker for olfactory marker protein. At the highest dose tested, cadmium exposure reduced the density of these projections by 20%. In a behavioral psychophysical task, mice were trained to sample from an odor port and make a response when they detected an odorant against a background of room air. After intranasal cadmium exposure, mice were unable to detect the target odor. These experiments serve as proof of concept for a new approach to the study of the neural effects of inhaled toxicants. The use of in vivo functional imaging of the neuronal populations exposed to the toxicant permits the direct observation of primary pathophysiology. In this study optical imaging revealed significant reductions in odorant-evoked release from the olfactory nerve at a cadmium chloride dose two orders of magnitude less than that required to induce morphological changes in the nerve in the same animals, demonstrating that it is a more sensitive technique for assessing the consequences of intranasal neurotoxicant exposure. This approach is potentially useful in exploring the effects of any putative neurotoxicant that can be delivered intranasally.     

PET-based investigation of cerebral activation following intranasal trigeminal stimulation

The present study aimed to investigate cerebral activation following intranasal trigeminal chemosensory stimulation using O15-H2O-PET. A total of 12 healthy male participants underwent a PET scan presented with four scanning conditions; two left-sided intranasal CO(2)-stimuli and two matched baseline conditions consisting of odorless air. CO(2) was used as it produces burning and stinging sensations. Stimulation started 20 s before intravenous injection of the isotope and lasted for the first 60 s of the 5 min scan time. A comparison between CO(2) and baseline showed a pronounced activation of the trigeminal projection area at the base of the postcentral gyrus (primary and secondary somatosensory cortex) which was more intense for the right hemisphere, contralateral to the side of stimulation. In addition, activation was also found in the piriform cortex which is typically activated following odor presentation and thus thought of as primary olfactory cortex. In conclusion, and in line with previously published work, our data suggest that intranasal trigeminal stimulation not only activates somatosensory projection areas, but that it also leads to activation in cerebral areas associated with the processing of olfactory information. This may be interpreted in terms of the intimate relation between the intranasal chemosensory systems.     

Somatosensory evoked potentials following stimulation of the trigeminal nerve in man

Summary Somatosensory evoked potentials following trigeminal nerve stimulation can regularly be recorded from the contralateral scalp on C5/C6 (10–20 system), a region which overlies the primary face region of the somatosensory cortex. From the first three peaks analyzed (N 13, P 19 and N26), the first positive peak (P 19) is most prominent and reliable and therefore is recommended for the routine measurements of neurophysiological examination.

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Zusammenfassung Nach der Stimulation des N. trigeminus am Mund lassen sich regelmäßig sensible evozierte Potentiale über dem kontralateralen somatosensorischen Cortex ableiten. Innerhalb der ersten 50 msec nach Reizbeginn treten typischerweise zwei negative und zwei positive Potentialschwankungen mit sehr variabler Amplitude auf. Aufgrund der an 55 Normalpersonen ermittelten mittleren Latenzzeiten kann der erste negative Gipfel als N 13, der erste positive Gipfel als P 19 und der zweite negative Gipfel als N 26 definiert werden. N 13 und P 19 zeigen eine Altersabhängigkeit mit leichter Latenzzunahme in der höheren Altersgruppe. P 19 ist wegen seiner konstanten Ausprägung für die klinische Diagnostik besonders geeignet.

     

Vasodilator responses following intracranial stimulation of the trigeminal, facial and glossopharyngeal nerves in the cat gingiva

The effects of electrical stimulation of the trigeminal, facial and glossopharyngeal nerves on gingival blood flow in the cat were studied. The intracranial part of these nerves was stimulated electrically, and gingival blood flow was measured by the laser Doppler technique. Electrical stimulation of the trigeminal, facial and glossopharyngeal nerves caused blood flow to increase in the ipsilateral gingiva both with the cranial nerve intact and after cutting it to the medulla. Stimulation of the distal cut ends of the facial and glossopharyngeal nerves elicited an increase in blood flow but no increase in systemic blood pressure. Pretreatment with hexamethonium reduced the increase in blood flow elicited by electrical stimulation of the facial and glossopharyngeal nerves, but had no effect on that elicited by stimulation of the trigeminal nerve. In contrast, pretreatment with tripelennamine attenuated the trigeminal nerve-stimulated blood flow increase, but not that elicited by stimulation of the facial and glossopharyngeal nerves. Atropine, propranolol and phentolamine had no effect on these responses. These results suggest that the autonomic nervous system, particularly the parasympathetic nervous system, is responsible for the blood flow increase elicited by facial and glossopharyngeal nerve stimulation, and that the trigeminal nerve-stimulated blood flow increase is induced by antidromic vasodilatation of the trigeminal sensory nerve.     

三叉神经体感诱发电位检测的改进

本文对正常80人采用上下唇表面电刺激记录了三叉神经诱发电位。记录电极安放在C_5’/C_6’(10～20系统Cz至外耳孔的中间点),参考电极安放在Fz点,刺激强度为感觉阈的3～4倍。其结果:刺激上唇在C_5’/C_6’点可记录到P_3、N_9、P_(20)、N_(25)、P_(35)、N_(45)各波,刺激下唇时在C_5’/C_6’,可记录到N_3、P_9、N_(13)、P_(20)、N_(25)、P_(35)、N_(45)各波。其记录方法简单,准确,易使被检者接受并在临床应用。     

Acute and long-term safety of external trigeminal nerve stimulation for drug-resistant epilepsy

Trigeminal nerve stimulation (TNS) is a novel therapy for drug-resistant epilepsy. We report in detail the safety of external TNS (eTNS), focusing on acute and long-term heart rate and systolic and diastolic blood pressure in response to TNS from the pilot feasibility study. The data indicate that eTNS of the infraorbital and supraorbital branches of the trigeminal nerve is safe and well tolerated.     

Responses of neurons in rostral and caudal trigeminal nuclei to tooth pulp stimulation

Using immobilized, lightly anesthetized cats, the responses of neurons in the nucleus principalis-subnucleus oralis and subnucleus caudalis regions of the sensory trigeminal complex were studied following electrical stimulation of the canine tooth pulp. Recording loci were verified histologically. Pulpal stimulation activated 122 cells in the rostral nuclei and 44 in the caudal one. Neurons in the two, spatially segregated, regions exhibited different, though overlapping distributions of response and receptive field properties. More specifically, the rostral region cells tended to have lower thresholds and to reach peak firing rates at lower stimulus intensities. Their peripheral fields were generally more restricted and more frequently homolateral. Following supra-maximal stimulation, they ordinarily had briefer initial spike latencies and their response bursts typically contained a greater number of spikes. These findings are consistent with the view that each of the regions operates in a different manner in the mediation of oro-facial pain.     

Substantia nigra unit responses to trigeminal sensory stimulation.

The influence of trigeminal sensory stimulation on substantia nigra units was investigated in cats anesthetized with chloralose. Low-intensity electrical stimulation was applied to primary sensory afferents (inferior dental nerve, trigeminal mesencephalic nucleus), and a high proportion of substantia nigra units showed evoked changes in activity. Responses were typically excitatory. Peripheral receptive fields were assessed by applying natural mechanosensory and also electrical stimulation to the face, perioral, and intraoral tissue. Substantia nigra units responded to light tactile stimuli; the majority of the receptive fields were bilateral, and all subsumed at least two branches of the trigeminal nerve. Latency considerations suggest that these sensory responses were not conveyed via striatonigral connections. The findings have implications in relation to the role of the basal ganglia, in general, in oropharyngeal sensorimotor processes.     

Comparative effects of stimulation of the trigeminal ganglion and the superior sagittal sinus on cerebral blood flow and evoked potentials in the cat

The superior sagittal sinus (SSS) and the trigeminal ganglion (Vg) of anesthetized cats were stimulated electrically and field potentials in the upper cervical spinal cord and regional cerebral blood flow were recorded. Stimulation of the entire ganglion produced smaller field potential changes in two regions (medioventral area (MVA); dorsolateral area (DLA] of the upper spinal cord than did stimulation of the sagittal sinus (Vg/SSS response ratio = 17% for the MVA and 48% for the DLA). Stimulation of the trigeminal ganglion increased blood flow in only the frontal and parietal cortices (+93% and +33%), whereas stimulation of the sinus produced both larger changes in these areas (+137% and +139%) and also produced changes in regional cerebral blood flow in the thalamus (+122%).     

Morphological and functional properties of trigeminal nucleus oralis neurons projecting to the trigeminal motor nucleus of the cat

Horseradish peroxidase (HRP) was injected into the somata located in the rostrodorsomedial part (Vo.r) of the trigeminal nucleus oralis; an axonal projection to the trigeminal motor nucleus (Vmo) was demonstrated in two Vo.r neurons. The two neurons differed in their morphological and functional properties. The first Vo.r neuron responded to stimulation of low-threshold mechanoreceptors and its stem axon gave off massive axon collaterals that issued terminal branches to the dorsolateral subdivision of Vmo, Vo.r, and the medial and lateral parts of the lower brainstem reticular formation. The second Vo.r neuron was activated by stimulation of the tooth pulp or lingual nerve at twice longer latency than that of the first neuron. This stem axon was divided into two main ascending and one descending branches, and one of the main ascending branches was further bifurcated into two branches. The main non-bifurcated ascending branch gave off 4 collaterals, two of which sent terminal branches into the dorsolateral subdivision of Vmo and others into the Vo.r and juxta-trigeminal regions. The somato-dendroarchitectonic differences were also described in the two Vo.r neurons stained.     

The neuronal correlates of intranasal trigeminal function—an ALE meta-analysis of human functional brain imaging data

Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO₂), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices—a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO₂ stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing.     

Rat trigeminal, olfactory and taste responses after capsaicin desensitization

Experiment 1 showed that capsaicin injections severely reduced or eliminated nasal trigeminal responses to 3 odorants. Experiments 2 and 3 investigated whether desensitized animals could behaviorally detect and discriminate odors. Capsaicin treated animals had no measurable deficits in locating buried food, in odor aversion learning, or in operant odor detection and discrimination. Experiment 4 examined whether behavioral responsiveness to salty, sour and bitter tastes was affected by desensitization. Capsaicin injections did not affect responsiveness to salty or sour, but may have raised rejection thresholds for bitter. Broadly, the present results suggest that substance P-containing fibers mediate trigeminal responsiveness to odorants and irritants but that the loss of this responsiveness does not appreciably affect smell or taste, per se.     

Ipsilateral trigeminal sensory responses to cortical stimulation by subdural electrodes

Twelve patients with medically intractable epilepsy had plates of chronic subdural electrodes placed over the lateral and basal cortical hemispheres during evaluations for surgical therapy. During cortical stimulation, ipsilateral sensations involving any of the branches of the trigeminal nerve were noted in the eye, face, and mouth. Some responses could have been due to dural or direct trigeminal nerve trunk stimulation, but others were probably due to electrical stimulation of trigeminal fibers accompanying the pial-arachnoidal vessels. These fibers had been demonstrated in animals, but not in humans.