Distribution of 5-HT1F Receptors in Monkey Vestibular and Trigeminal Ganglion Cells

Background: Evidence of serotonergic involvement in vestibular pathway contributions to migraine and balance disorders is compelling. Serotonergic 5-HT1B and 5-HT1D receptors are expressed extensively in inner ear ganglia of monkeys and rats. The serotonergic 5-HT1F receptor is also a target of triptans. This study describes its distribution in vestibular and trigeminal ganglia of monkeys. Methods: Using primary polyclonal antibodies raised against oligopeptides specific for the human 5-HT1F receptor, neuronal somatic area and intensity of immunoreactive vestibular and trigeminal ganglia were quantified. Results and Discussion: Virtually all vestibular and considerable trigeminal ganglia showed positive 5-HT1F receptor immunoreactivity. Inferior and superior vestibular ganglia staining appeared confined to distinct cell regions, varying considerably among cells of different sizes: more intense in small, punctate in some medium and regionally polarized in some large cells. Analyses of average somatic vestibular neuronal immunoreactive intensity identified mainly medium sized cells with high standard deviation of intensity corresponding to punctately-stained cells. Less variability occurred in somatic intensity staining and cellular distribution among 5-HT1F receptor immunopositive trigeminal ganglia. Most exhibited similar punctate staining patterns, higher mean somatic immunoreactive intensity and larger neuronal somatic size proportions per size distribution subpopulation compared to vestibular ganglia size distribution populations. Centrally directed vestibular ganglion neuronal processes, cochlear inner hair cells, vestibular hair cells and blood vessels in vestibular maculae and cristae were immunoreactive. The 5-HT1F receptor expression in vestibular ganglia shows complex variable staining intensity patterns associated with cell size of immunopositive neurons, not seen in immunopositive trigeminal ganglia and not previously evident with 5-HT1B and 5-HT1D receptor subtype immunoreactivity in vestibular ganglia. These data motivate exploration of 5-HT1 receptor oligomerization and ligand functional selectivity in differential serotonergic involvement in co-morbidity of migraine and balance disorders. Similar findings in cochlear inner hair cell afferents are applicable to migraine related tinnitus or hypercusis (phonophobia)

Patterns of Pupillary Activity During Binocular Disparity Resolution

This study examined the dynamic coordination between disconjugate, vergence eye movements, and pupil size in 52 normal subjects during binocular disparity stimulation in a virtual reality display. Eye movements and pupil area were sampled with a video-oculographic system at 100 Hz during performance of two tasks, (1) fusion of a binocular disparity step (±1.5° of visual angle in the horizontal plane) and (2) pursuit of a sinusoidally varying binocular disparity stimulus (0.1 Hz, ±2.6° of visual angle in the horizontal plane). Pupil size data were normalized on the basis of responses to homogeneous illumination increments ranging from 0.42 to 65.4 cd/m2. The subjects produced robust vergence eye movements in response to disparity step shifts and high fidelity sinusoidal vergence responses (R2 relative to stimulus profile: 0.933 ± 0.088), accompanied by changes in pupil area. Trajectory plots of pupil area as a function of vergence angle showed that the pupil area at zero vergence is altered between epochs of linear vergence angle—pupil area relations. Analysis with a modified Gath-Geva clustering algorithm revealed that the dynamic relationship between the ocular vergence angle and pupil size includes two different transient, synkinetic response patterns. The near response pattern, pupil constriction during convergence and pupil dilation during divergence, occurred ~80% of the time across subjects. An opposite, previously undescribed synkinetic pattern was pupil constriction during divergence and pupil dilatation during convergence; it occurred ~15% of the time across subjects. The remainder of the data were epochs of uncorrelated activity. The pupil size intercepts of the synkinetic segments, representing pupil size at initial tropia, had different relationships to vergence angle for the two main coordinated movement types. Hippus-like movements of the pupil could also be accompanied by vergence movements. No pupil coordination was observed during a conjugate pursuit task. In terms of the current dual interaction control model (1), findings suggest that the synkinetic eye and pupillary movements are produced by a dynamic switch of the influence of vergence related information to pupil control, accompanied by a resetting of the pupil aperture size at zero-vergence

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation

Motion sickness is a complex condition that includes both overt signs (e.g., vomiting) and more covert symptoms (e.g., anxiety and foreboding). The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos)-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activated during this stimulus paradigm from functional correlations between Fos labeling in different nuclei. This analysis identified five principal components (neural networks) that accounted for greater than 95% of the variance in Fos labeling. Two of the components were correlated with the severity of motion sickness symptoms, and likely participated in generating the overt signs of the condition. One of these networks included neurons in locus coeruleus, medial, inferior and lateral vestibular nuclei, lateral nucleus tractus solitarius, medial parabrachial nucleus and periaqueductal gray. The second included neurons in the superior vestibular nucleus, precerebellar nuclei, periaqueductal gray, and parabrachial nuclei, with weaker associations of raphe nuclei. Three additional components (networks) were also identified that were not correlated with the severity of motion sickness symptoms. These networks likely mediated the covert aspects of motion sickness, such as affective components. The identification of five statistically independent component networks associated with the development of motion sickness provides an opportunity to consider, in network activation dimensions, the complex progression of signs and symptoms that are precipitated in provocative environments. Similar methodology can be used to parse the neural networks that mediate other complex responses to environmental stimuli. © 2014 Balaban et al

Consequence of one-electron oxidation and one-electron reduction for aniline

Quantum-chemical calculations were performed for all possible isomers of neutral aniline and its redox forms, and intramolecular proton-transfer (prototropy) accompanied by π-electron delocalization was analyzed. One-electron oxidation (PhNH2 – e → [PhNH2]+•) has no important effect on tautomeric preferences. The enamine tautomer is preferred for oxidized aniline similarly as for the neutral molecule. Dramatical changes take place when proceeding from neutral to reduced aniline. One-electron reduction (PhNH2 + e → [PhNH2]-•) favors the imine tautomer. Independently on the state of oxidation, π- and n-electrons are more delocalized for the enamine than imine tautomers. The change of the tautomeric preferences for reduced aniline may partially explain the origin of the CH tautomers for reduced nucleobases (cytosine, adenine, and guanine)

All Needs Approach to Emergency Response

This article appeared in Homeland Security Affairs (February 2012), v.8, article 1"For decades, emergency planners have operated either under an approach termed '''all hazards,'۪ focusing on the commonalities of catastrophes, or under scenario-specific planning rubrics that aligned actions with the particular cause of the disaster. While each method has its strengths and advocates, both have demonstrated shortcomings in execution and generated pervasive dissatisfaction among served communities. The authors contend this discontent derives from a failure to address the perceived needs within the impacted populations. Drawing upon classic theories of rationality and motivation, a new paradigm of '''all needs'۪ planning is proposed. This approach offers an effective planning matrix that is both flexible and robust in assessing the myriad needs of a disaster-stricken populace.