Resolving the active versus passive conundrum for head direction cells.

Head direction (HD) cells have been identified in a number of limbic system structures. These cells encode the animal's perceived directional heading in the horizontal plane and are dependent on an intact vestibular system. Previous studies have reported that the responses of vestibular neurons within the vestibular nuclei are markedly attenuated when an animal makes a volitional head turn compared to passive rotation. This finding presents a conundrum in that if vestibular responses are suppressed during an active head turn how is a vestibular signal propagated forward to drive and update the HD signal? This review identifies and discusses four possible mechanisms that could resolve this problem. These mechanisms are: (1) the ascending vestibular signal is generated by more than just vestibular-only neurons, (2) not all vestibular-only neurons contributing to the HD pathway have firing rates that are attenuated by active head turns, (3) the ascending pathway may be spared from the affects of the attenuation in that the HD system receives information from other vestibular brainstem sites that do not include vestibular-only cells, and (4) the ascending signal is affected by the inhibited vestibular signal during an active head turn, but the HD circuit compensates and uses the altered signal to accurately update the current HD. Future studies will be needed to decipher which of these possibilities is correct.

Vestibular efferent neurons project to the flocculus.

A bilateral projection from the vestibular efferent neurons, located dorsal to the genu of the facial nerve, to the cerebellar flocculus and ventral paraflocculus was demonstrated. Efferent neurons were double-labeled by the unilateral injections of separate retrograde tracers into the labyrinth and into the floccular and ventral parafloccular lobules. Efferent neurons were found with double retrograde tracer labeling both ipsilateral and contralateral to the sites of injection. No double labeling was found when using a fluorescent tracer with non-fluorescent tracers such as horseradish peroxidase (HRP) or biotinylated dextran amine (BDA), but large percentages of efferent neurons were found to be double labeled when using two fluorescent substances including: fluorogold, microruby dextran amine, or rhodamine labeled latex beads. These data suggest a potential role for vestibular efferent neurons in modulating the dynamics of the vestibulo-ocular reflex (VOR) during normal and adaptive conditions.

Convergent properties of vestibular-related brain stem neurons in the gerbil.

Three classes of vestibular-related neurons were found in and near the prepositus and medial vestibular nuclei of alert or decerebrate gerbils, those responding to: horizontal translational motion, horizontal head rotation, or both. Their distribution ratios were 1:2:2, respectively. Many cells responsive to translational motion exhibited spatiotemporal characteristics with both response gain and phase varying as a function of the stimulus vector angle. Rotationally sensitive neurons were distributed as Type I, II, or III responses (sensitive to ipsilateral, contralateral, or both directions, respectively) in the ratios of 4:6:1. Four tested factors shaped the response dynamics of the sampled neurons: canal-otolith convergence, oculomotor-related activity, rotational Type (I or II), and the phase of the maximum response. Type I nonconvergent cells displayed increasing gains with increasing rotational stimulus frequency (0.1-2.0 Hz, 60 degrees /s), whereas Type II neurons with convergent inputs had response gains that markedly decreased with increasing translational stimulus frequency (0.25-2.0 Hz, +/-0.1 g). Type I convergent and Type II nonconvergent neurons exhibited essentially flat gains across the stimulus frequency range. Oculomotor-related activity was noted in 30% of the cells across all functional types, appearing as burst/pause discharge patterns related to the fast phase of nystagmus during head rotation. Oculomotor-related activity was correlated with enhanced dynamic range compared with the same category that had no oculomotor-related response. Finally, responses that were in-phase with head velocity during rotation exhibited greater gains with stimulus frequency increments than neurons with out-of-phase responses. In contrast, for translational motion, neurons out of phase with head acceleration exhibited low-pass characteristics, whereas in-phase neurons did not. Data from decerebrate preparations revealed that although similar response types could be detected, the sampled cells generally had lower background discharge rates, on average one-third lower response gains, and convergent properties that differed from those found in the alert animals. On the basis of the dynamic response of identified cell types, we propose a pair of models in which inhibitory input from vestibular-related neurons converges on oculomotor neurons with excitatory inputs from the vestibular nuclei. Simple signal convergence and combinations of different types of vestibular labyrinth information can enrich the dynamic characteristics of the rotational and translational vestibuloocular responses.

Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation.

Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation.

Soft tissue calcifications induced by local corticosteroid injection.

The authors discuss soft tissue calcifications as a possible effect of local corticosteroid therapy. The literature will be reviewed and a case report will be presented, which illustrates soft tissue calcifications in the heel of a patient who received multiple injections of triamcinolone hexacetonide, for heel spur syndrome. The accumulation of insoluable steroid acts as a foreign body and induced a chronic granulomatous inflammatory process, with subsequent dystrophic calcification.

Unicameral bone cyst of the talus.

The authors present a rare case of a talar unicameral bone cyst in a 9-year-old boy. This is the first such case presented in podiatric literature; the lesion has been cited infrequently in world literature. A brief review of the literature is discussed, along with the diagnostic tests, possible complications, and proper therapy for this lesion.