Discovering a new functional neurogenic zone: the vestibular nuclei of the brainstem

The adult mammal brain is mostly considered as non-neurogenic, except in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus, where ongoing neurogenesis occurs. However, anti-neurogenic influences can be removed in pathological conditions or after specific injury. That is what happens in a model of unilateral vestibular neurectomy (UVN) that mimics human pathology in adult cats. We showed for the first time that a UVN promoted an intense reactive cell proliferation in the deafferented vestibular nuclei located in the brainstem. The new cells survived up to one month, differentiated into glial cells - microglia or astrocytes - or GABAergic neurons, so highlighting a GABAergic neurogenesis. Surprisingly, we further showed that post-UVN reactive cell proliferation contributed successfully to fine restoration of vestibular posturo-locomotor functions. In conclusion, these pioneering studies bring new pieces of a promising puzzle in both stem cell and vestibular therapy domains.     

Molecular mechanisms of Brainstem plasticity

Vestibular compensation is the process of behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (unilateral labyrinthectomy, UL). Since UL results in a permanent loss of vestibular input from the ipsilateral vestibular (VIIIth) nerve, vestibular compensation is attributed to CNS plasticity and has been used as a general model of lesion-induced CNS plasticity. Behavioral recovery from the ocular motor and postural symptoms of UL is correlated with a partial return of resting activity to neurons in the vestibular nucleus (VN) on the deafferented side (the "deafferented VN"), and lesions to the deafferented VN prevent compensation; therefore, the regeneration of resting activity within the deafferented VN is believed to have a causal role in vestibular compensation. The biochemical mechanisms responsible for the adaptive neuronal changes within the deafferented VN are poorly understood. Neuropeptide hormone fragments, such as adrenocorticotrophic hormone (ACTH)-4-10, have been shown to accelerate vestibular compensation and can act directly on some VN neurons in vitro. Antagonists for the N-methyl-D-aspartate (NMDA) receptor have been shown to inhibit vestibular compensation if administered early in the compensation process. Biochemical studies in frog indicate marked alterations in the phosphorylation patterns of several proteins during compensation, and the in vitro phosphorylation of some of these proteins is modulated by ACTH-(1-24), calcium (Ca2+), and calmodulin or protein kinase C. It is therefore possible that ACTH fragments and NMDA antagonists (via their effects on NMDA receptor-mediated Ca2+ channels) modulate vestibular compensation through their action on Ca(2+)-dependent pathways within VN neurons. Recent studies have shown that some Ca2+ channel antagonists and the Ca(2+)-dependent enzyme inhibitor calmidazolium chloride facilitate vestibular compensation. How the regulation of Ca2+ may be related to the neuronal changes responsible for vestibular compensation is unclear at present.     

Excitatory amino acid receptors in normal and abnormal vestibular function

Although excitatory amino acid (EAA) receptors have been investigated extensively in the limbic system and neocortex, less is known of the function of EAA receptors in the brainstem. A number of biochemical and electrophysiological studies suggest that the synapse between the ipsilateral vestibular (VIIIth) nerve and the brainstem vestibular nucleus (VN) is mediated by an EAA acting predominantly on kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. In addition, there is electrophysiological evidence that input from the contralateral vestibular nerve via the contralateral VN is partially mediated by N-methyl-D-aspartate (NMDA) receptors. Input to the VN from the spinal cord may also be partially mediated by NMDA receptors. All of the electrophysiological studies conducted so far have used in vitro preparations, and it is possible that denervation of the VN during the preparation of an explant or slice causes changes in EAA receptor function. Nonetheless, these results suggest that EAA receptors may be important in many different parts of the vestibular reflex pathways. Studies of the peripheral vestibular system have also shown that EAAs are involved in transmission between the receptor hair cells and the vestibular nerve fibers. A number of recent studies in the area of vestibular plasticity have reported that antagonists for the NMDA receptor subtype disrupt the behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (vestibular compensation). It has been suggested that vestibular compensation may be owing to an upregulation or increased affinity of NMDA receptors in the VN ipsilateral to the peripheral deafferentation; however; at present, there is no clear evidence to support this hypothesis.     

前庭功能的中枢组胺能神经调制

组胺能药物已经长期用于治疗人类的平衡紊乱,但对于它们在前庭系统中作用的机制还缺乏了解。在本文中,我们综述了关于脑内（特别是脑干前庭核中）的组胺能神经传递,以及组胺在脑可塑性——“前庭代偿”（一种单侧外周前庭损伤之后发生的行为学恢复）中作用的新近文献。我们在综述组胺能类药物促进前庭代偿证据的同时,也讨论了这类药物临床应用的可能性。     

Acetyl—DL—leucine对猫单侧前庭神经切断后运动平衡能力和前庭外…

本文观测了Ａｃｅｔｙｌ－ＤＬ－ｌｅｕｃｉｎｅ对猫单侧前庭神经切断后前庭代偿的影响。结果显示;ＡＬ加快术后猎在转动横梁测试中运动平衡能力的恢复,但抑制去传入前庭外侧核神经元静息自发放电频率的恢复。ＡＬ促进放电活动与头部左右动体位相关的神经元数量和比例的恢复,从术后的第１周的１０％,逐渐提高到术后第３周的６０％。第５周的７５％。     

Effects of unilateral labyrinthectomy on the norepinephrine content in forebrain and cerebellar structures of albino rats

Albino (Wistar) rats were used to investigate whether unilateral labyrinthectomy (UL) modified the concentration of norepinephrine (NE) as well as of dopamine (DA) and the corresponding metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in different areas of the cerebral and the cerebellar cortex and the striatum. The results obtained in 38 rats submitted to UL were compared to those of 18 rats submitted to sham-operation. The animals were operated under sodium pentobarbital anesthesia and sacrificed 1.5, 3 and 6 h after surgery. All rats submitted to UL showed phenomena of deficit (1.5-3 h after the lesion) followed by partial vestibular compensation (3-6 h after the lesion). Significant changes in the content of NE were neither found in different areas of the cerebral and the cerebellar cortex, nor in the striatum of rats sacrificed 1.5 h after UL. Three h after the lesion a bilateral increase in the NE content occurred in all the explored areas of the cerebral cortex (i.e., frontal, parieto-temporal and occipital) and the cerebellar cortex (i.e., the vermis and flocculus), as well as in the striatum. This increase, however, was more prominent in the parieto-temporal areas of the neocortex of the intact side, in all the explored areas of the cerebellar cortex of that side, as well as in the striatum of the lesioned side. This asymmetric increase in NE content could not be attributed, at least exclusively, to a generalized activation of the noradrenergic LC nuclei of both sides, due to waking and/or stress which may occur after UL, but did rather depend on asymmetric changes in unit discharge of the vestibular nuclei projecting to the LC of both sides, following UL. In particular, the increased discharge of the vestibular nuclei of the intact side would lead to activation of noradrenergic neurons projecting particularly to the parieto-temporal cortex and the cerebellar cortex of the intact side, as well as to the striatum of the lesioned side. A bilateral increase in NE content was still observed in different areas of the cerebral and cerebellar cortex of rats sacrificed 6 h after UL. This increase, however, was of smaller entity than that observed in the same areas 3 h after UL and quite symmetric. The content of DA and its metabolite DOPAC decreased bilaterally in the striatum of rats sacrificed 1.5 h after UL. This effect was attributed to a reduced synthesis and release of DA, which probably resulted from a reduced facilitatory influence that the deafferented vestibular nuclei exert on the dopaminergic, nigrostriatal system of both sides, although mainly on the intact side. The corresponding values, however, bilaterally recovered to slightly increase with respect to the control values in rats sacrificed 3 and 6 h after UL. In these experiments the content of both DA and DOPAC remained symmetric on both sides after UL, in contrast with the bilateral but asymmetric increase in NE concentration observed in the same structure 3 h the lesion. The present results integrate and extend those of previous experiments showing that: 1) albino rats sacrificed 6 h after UL displayed an increased synthesis of NE, which affected particularly the LC of the intact side as well as the medial vestibular nuclei of both sides (21); and 2) the structures which showed an increased content of NE at given time intervals after UL also displayed an increase in the expression of the immediate early gene c-fos (cf. 16 for ref.). These findings suggest that bilateral but asymmetric activation of the noradrenergic LC neurons following UL may lead to an asymmetric increase in c-fos expression in several target structures, thus contributing to the plastic changes responsible for vestibular compensation. In conclusion, it appears that UL induces in several brain structures of albino rats a short-term increase in synthesis and release of NE. (ABSTRACT TRUNCATED)     

单侧迷路破坏后大鼠前庭神经内侧核区氨基酸含量的变化

本实验用脑部微量透析法和高效液相色谱法观察单侧迷路破坏(unilateral labyrinthectomy,经利多卡因或对氨基苯胂酸盐预处理以阻断单侧外周前庭器官)后大鼠同侧及对侧前庭神经内侧核(medial vestibular nucleus,MVN)区部分氨基酸(天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、牛磺酸和丙氨酸)含量的变化,以了解前庭代偿的部分神经化学机制.实验观察到,对照组大鼠MVN区天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、牛磺酸和丙氨酸浓度分别为(6.15±0.59),(18.13±1.21),(33.73±1.67),(9.26±0.65),(9.56±0.77)和(10.07±0.83)pmol/8 μL透析样本.左侧中耳内灌注2%利多卡因后10 min,同侧MVN区天冬氨酸、谷氨酸含量立即减少(P＜0.05),牛磺酸含量增加(P＜0.05);对侧MVN区谷氨酸含量立即增加(P＜0.05),甘氨酸和丙氨酸含量减少;双侧核团间谷氨酸、甘氨酸和丙氨酸含量失衡.而用对氨基苯胂酸盐永久阻断单侧前庭器官2周后,同侧MVN区谷氨酸和丙氨酸含量减少,谷氨酰胺含量增高;对侧MVN区谷氨酸含量也减少;同侧MVN区谷氨酰胺含量明显高于对侧MVN区.结果提示,单侧迷路破坏后双侧MVN区氨基酸含量立即失去平衡,随着前庭代偿的进展,此差异减少,但是在前庭代偿后却出现双侧前庭核区谷氨酰氨的含量失衡,说明在前庭代偿过程中氨基酸含量变化起着重要作用.     

Effect of auditory deafferentation on the synaptic connectivity of a pair of identified interneurons in adult field crickets

In adult crickets, Teleogryllus oceanicus, unilateral auditory deafferentation causes the medial dendrites of an afferent-deprived, identified auditory interneuron (Int-1) in the prothoracic ganglion to sprout and form new functional connections in the contralateral auditory neuropil. The establishment of these new functional connections by the deafferented Int-1, however, does not appear to affect the physiological responses of Int-1's homolog on the intact side of the prothoracic ganglion which also innervates this auditory neuropil. Thus it appears that the sprouting dendrites of the deafferented Int-1 are not functionally competing with those of the intact Int-1 for synaptic connections in the remaining auditory neuropil following unilateral deafferentation in adult crickets. Moreover, we demonstrate that auditory function is restored to the afferent-deprived Int-1 within 4-6 days following deafferentation, when few branches of Int-1's medial dendrites can be seen to have sprouted. The strength of the physiological responses and extent of dendritic sprouting in the deafferented Int-1 progressively increase with time following deafferentation. By 28 days following deafferentation, most of the normal physiological responses of Int-1 to auditory stimuli have been restored in the deafferented Int-1, and the medial dendrites of the deafferented Int-1 have clearly sprouted and grown across into the contralateral auditory afferent field. The strength of the physiological responses of the deafferented Int-1 to auditory stimuli and extent of dendritic sprouting in the deafferented Int-1 are greater in crickets deafferented as juveniles than as adults. Thus, neuronal plasticity persists in Int-1 following sensory deprivation from the earliest juvenile stages through adulthood.     

Testable predictions from realistic neural network simulations of vestibular compensation: integrating the behavioural and physiological data

Neural network simulations have been used previously in the investigation of the horizontal vestibulo-ocular reflex (HVOR) and vestibular compensation. The simulations involved in the present research were based on known anatomy and physiology of the vestibular pathway. This enabled the straightforward comparison of the network response, both in terms of behavioural (eye movement) and physiological (neural activity) data to empirical data obtained from guinea pig. The network simulations matched the empirical data closely both in terms of the static symptoms (spontaneous nystagmus) of unilateral vestibular deafferentation (UVD) as well as in terms of the dynamic symptoms (decrease in VOR gain). The use of multiple versions of the basic network, trained to simulate individual guinea pigs, highlighted the importance of the particular connections: the vestibular ganglion to the type I medial vestibular nucleus (MVN) cells on the contralesional side. It also indicated the significance of the relative firing rate in type I MVN cells which make excitatory connections with abducens cells as contributors to the variability seen in the level of compensated response following UVD. There was an absence of any difference (both in terms of behavioural and neural response) between labyrinthectomised and neurectomised simulations. The fact that a dynamic VOR gain asymmetry remained following the elimination of the spontaneous nystagmus in the network suggested that the amelioration of both the static and dynamic symptoms of UVD may be mediated by a single network. The networks were trained on high acceleration impulse stimuli but displayed the ability to generalise to low frequency, low acceleration sinusoids and closely approximated the behavioural responses to those stimuli. Received: 12 October 1998 / Accepted in revised form: 11 February 1999     

A neural network simulation of the vestibular system: implications on the role of intervestibular nuclear coupling during vestibular compensation

 Previous neural network simulations of the vestibular system have been based loosely on known physiology. This research involved the use of a strongly physiologically based neural network model which was used to investigate the role of the vestibular commissure in restoring the bilateral symmetry of the resting rates of the vestibular nuclei during vestibular compensation following unilateral labyrinthectomy. It was found that readjustments in the gain of the vestibular commissure were not primarily responsible for vestibular compensation, as has previously been suggested, but rather that it was modifications in extralabyrinthine sources of tone which mediated the restoration of the central symmetry between the two nuclei. Received: 20 November 1995/Accepted in revised form: 24 July 1996     

Inferior vestibular neuritis: 3 cases with clinical features of acute vestibular neuritis, normal calorics but indications of saccular failure

Background  

Vestibular neuritis (VN) is commonly diagnosed by demonstration of unilateral vestibular failure, as unilateral loss of caloric response. As this test reflects the function of the superior part of the vestibular nerve only, cases of pure inferior nerve neuritis will be lost.     

Effects of bilateral vestibular nucleus lesions on cardiovascular regulation in conscious cats.

The vestibular system participates in cardiovascular regulation during postural changes. In prior studies (Holmes MJ, Cotter LA, Arendt HE, Cas SP, and Yates BJ. Brain Res 938: 62-72, 2002, and Jian BJ, Cotter LA, Emanuel BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999), transection of the vestibular nerves resulted in instability in blood pressure during nose-up body tilts, particularly when no visual information reflecting body position in space was available. However, recovery of orthostatic tolerance occurred within 1 wk, presumably because the vestibular nuclei integrate a variety of sensory inputs reflecting body location. The present study tested the hypothesis that lesions of the vestibular nuclei result in persistent cardiovascular deficits during orthostatic challenges. Blood pressure and heart rate were monitored in five conscious cats during nose-up tilts of varying amplitude, both before and after chemical lesions of the vestibular nuclei. Before lesions, blood pressure remained relatively stable during tilts. In all animals, the blood pressure responses to nose-up tilts were altered by damage to the medial and inferior vestibular nuclei; these effects were noted both when animals were tested in the presence and absence of visual feedback. In four of the five animals, the lesions also resulted in augmented heart rate increases from baseline values during 60 degrees nose-up tilts. These effects persisted for longer than 1 wk, but they gradually resolved over time, except in the animal with the worst deficits. These observations suggest that recovery of compensatory cardiovascular responses after loss of vestibular inputs is accomplished at least in part through plastic changes in the vestibular nuclei and the enhancement of the ability of vestibular nucleus neurons to discriminate body position in space by employing nonlabyrinthine signals.     

Lesion‐induced neurogenesis in the hypothalamus is involved in behavioral recovery in adult ring doves

Although neurogenesis in the brain of adult vertebrates is region dependent, lesion induces generation of new neurons in non‐neurogenic brain regions. These findings raise the question of the role of new neurons in brain repair and functional recovery. We addressed this question by applying previous observations that electrolytic lesion induced neurogenesis in the ventromedial nucleus (VMN) of the hypothalamus in adult ring doves. Such lesions disrupted the male's courtship behavior, which could be reinstated after rehabilitation with a female. We investigated whether lesion‐induced newborn neurons in the VMN facilitate the recovery of courtship behavior in the lesioned birds. We conducted systematic observations of cytological, morphological, and neuroanatomical changes in the lesioned VMN, and concurrently we monitored behavioral changes. Using a multitude of specific cell markers, we found a well‐circumscribed cellular zone that proliferated actively. This highly proliferative zone initially appeared along the periphery of the lesion site, where cells had high levels of expression of neuronal, glial, and neurovascular markers. As newborn neurons matured at the lesion site, the necrosis gradually decreased, whereas a downsized proliferative zone relocated to a region ventral to the VMN. Some of the mature neurons were found to project to the midbrain vocal nuclei. Restoration of these projection neurons coincided with the recovery of courtship vocalization. Finally, we found that a social factor, that is, when the male doves were cohoused with a mate, facilitated neurogenesis and behavioral recovery. These results suggest that lesion‐induced neurogenesis contributes to behavioral recovery in adult animals. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006     

Morphological and electrophysiological consequences of unilateral pre- versus postganglionic vestibular lesions in the frog

The combined removal of the labyrinthine sense organs and of the ganglion of Scarpa on one side (postganglionic section) resulted in a degeneration of afferent fibres in the eighth nerve of the frog (Rana temporaria) within 2–4 days. If the eighth nerve was sectioned more peripherally (preganglionic section) and its distal part was removed together with the labyrinthine organs degeneration of afferent fibres was absent or restricted to very few fibres. Electrical stimulation of vestibular afferents in vitro evoked monosynaptic field potentials in the ipsilateral and via commissural fibres di-and polysynaptic field potentials in the contralateral vestibular nuclei. Afferent-evoked field potentials recorded on the intact side of chronic frogs ( 60 days) with a preor postganglionic lesion and afferent-evoked field potentials recorded on the operated side of chronic frogs with a preganglionic lesion had amplitudes that were very similar to those recorded in control frogs. Commissurally evoked field potentials recorded on the operated side of chronic frogs with preor postganglionic lesions were significantly increased (by about 90%) with respect to control amplitudes. In both groups the time-course of this increase was very similar, started between 15 and 30 days and saturated for survival periods longer than 60 days. Unilateral inactivation of vestibular afferents, but not degeneration, is the likely common denominator of the central process leading to the reported neural changes. A reactive supersensitivity of central vestibular neurons on the operated side for glutamate as a possible mechanism is unlikely, since converging afferent and commissural inputs are both glutamatergic and only one of them, the commissural input, was potentiated. Comparison of the time-courses of neural changes in the vestibular nuclei and postural recovery in the same individuals excludes a causal relation between both phenomena.Abbreviations HL hemilabyrinthectomy - VNC vestibular nuclear complex - HRP horseradish peroxidase - N. VIII eighth nerve - N. IX ninth nerve     

Changes in extracellular levels of dopamine metabolites in somatosensory cortex after peripheral denervation

This study examined the effects of a nerve transection on monoamine release from primary somatosensory cortex. The technique of microdialysis was employed to sample extracellular levels of norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the barrel field of freely moving rats following the surgical transection of the contralateral infraorbital nerve. Microdialysates obtained 3, 4, and 5 days after deafferentation were analyzed using high-performance liquid chromatography with electrochemical detection. We found a significant increase in the release of the dopamine metabolites, DOPAC and HVA from the deafferented cortex. Three days after deafferentation the release of DOPAC was three-fold higher in the deafferented than in the control animals, and remained about 100% higher in the next two days in this group of animals. The release of HVA showed a gradual increase following the deafferentation procedure, since a 92% larger value on day 3 increased to a 338% difference on day 5. On the other hand, the release rate of NE and the levels of the serotonin metabolite 5-HIAA were not significantly affected by the deafferentation procedure. These results are discussed in the context of the possible participation of dopamine in the reorganization of the deafferented somatosensory cortex.     

Microarray analysis of gene expression in the rat vestibular nucleus complex following unilateral vestibular deafferentation

To investigate the molecular background of vestibular compensation, a model of lesion-induced plasticity, we used a microarray analysis to examine genes that show asymmetrical expression between the bilateral vestibular nucleus complexes (VNCs) 6 h following unilateral vestibular deafferentation (UVD). Asymmetrical gene expression was then validated by a real-time quantitative PCR. Among the 88 genes for which the ipsilateral (ipsi) : contralateral (contra) was > 1.35, the number of known genes was 33 (38%), and the number of expressed sequence tag (EST) sequences was 55 (62%). Among the 130 genes for which the contra : ipsi was > 1.35, the number of known genes was 55 (42%), and the number of EST sequences was 75 (58%). Changes in some of the genes were consistent with previous studies; however, we found several new genes which could be functionally related to the molecular basis of the electrophysiological asymmetry between the VNCs following UVD. Ipsi > contra genes included the GABA(A) receptor rho subunit, regulatory proteins of G protein signaling, calcium signaling related molecules such as the voltage-dependent calcium channel alpha2/delta subunit 1, calcineurin subunit Abeta and Ca(2+) pump. Contra > ipsi genes included the neuronal high affinity glutamate transporter, 5-hydroxytryptamine receptor 1D, mitogen-activated protein kinase 12 and ubiquitin carboxy-terminal hydrolase L1.     

Protective Effects of Hypothalamic Proline-Rich Peptide and Cobra Venom Naja Naja Oxiana on Dynamics of Vestibular Compensation Following Unilateral Labyrinthectomy

We tested the action of proline-rich peptide (PRP-1) and cobra venom Naja Naja Oxiana (NOX) on Deiters’ nucleus neurons at 3rd, 15th and 35th days after unilateral labyrinthectomy (UL). Early and late tetanic, post-tetanic potentiation and depression of Deiters’neurons to bilateral high frequency stimulation of hypothalamic supraoptic and paraventricualar nuclei was studied. The analysis of spike activity was carried out by mean of on-line selection and special program. The complex averaged peri-event time and frequency histograms shows the increase of inhibitory and excitatory reactions of Deiters’ neurons at early stage of vestibular compensation following PRP-1 and NOX injection, reaching the norm at the end of tests. In histochemical study the changes in Ca²⁺-dependent acidic phosphatase (AP) activity in neurons was discovered. It was shown that in UL animals the total disappearance or delay of decolorizing of Deiters’ neurons lead to neurodegenerative pattern as cellular “shade”. AP activity after UL and PRP-1 injection exerts more effective recovery of neurons in comparison with events, observed after the administration of NOX. The data of this study indicate that PRP-1 and NOX are protectors, which may successfully recover the disturbed vestibular functions.     

Afferent connections of the cat lateral vestibular nucleus

Location within the brain of HP-labeled neurons (origins of projections to the lateral vestibular nucleus) was investigated by iontophoretic injection of this enzyme. Bilateral projections to the following midbrain structures were revealed: the field of Forel, interstitial nuclei of Cajal, oculomotor nerve nuclei, and the red nucleus — to all parts of the lateral vestibular nucleus. Bilateral projections were also shown from more caudally located structures, viz. the superior, medial and inferior (descending) vestibular nuclei, Y groups of the vestibular nuclear complex, facial nucleus and hypoglossi, nucleus prepositus nervi hypoglossi and caudal nuclei of the trigeminal tract; ipsilateral projections from crus IIa of lobulus ansiformus of the cerebellar hemisphere; contralateral projections from the bulbar lateral reticular nucleus and Deiter's nucleus. A tonic organization pattern of afferent inputs from a number of brainstem formations to the dorsal and ventral lateral vestibular nucleus is revealed and trajectories of HP-labeled fiber systems projecting to Deiter's nucleus described.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 20, No. 4, pp. 494–503, July–August, 1988.     

Histological changes in the somatosensory thalamus after unilateral coagulation of vibrissa follicles of the muzzle of the newborn mouse

Light microscopic study of the thalamic ventro-basal complex (VB), after unilateral coagulation of vibrissae follicles in newborn mouse, revealed an excess of neuronal perikarya on the controlateral "deafferented" side as compared to the normal side. The higher density of nerve cells was confined to the vibrissal relay in the medial part of VB nucleus (VBm), whereas the cell number in the non vibrissal-lateral part of this nucleus (VB1) remained on the control level. Electron microscopic investigation of the thalamic vibrissal relay has shown signs of a modified synaptogenesis on the "deafferented" side: (a) the number of specific afferents has diminished and in contrast to the normal side, most of the specific sensory terminals contain small spheroid synaptic vesicles and (b) the number of axon terminals with ovoid pleomorphic vesicles has been doubled.     

Changes in Histamine Receptors (H1, H2, and H3) Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation

Vestibular compensation is the process of behavioral recovery following peripheral vestibular lesion. In clinics, the histaminergic medicine is the most widely prescribed for the treatment of vertigo and motion sickness, however, the molecular mechanisms by which histamine modulates vestibular function remain unclear. During recovery from the lesion, the modulation of histamine receptors in the medial vestibular nucleus (MVN) and the flocculus may play an important role. Here with the means of quantitative real-time PCR, western blotting and immunohistochemistry, we studied the expression of histamine receptors (H1, H2, and H3) in the bilateral MVN and the flocculus of rats on the 1st, 3rd, and 7th day following unilateral labyrinthectomy (UL). Our results have shown that on the ipsi-lesional flocculus the H1, H2 and H3 receptors mRNA and the protein increased significantly on the 1st and 3rd day, with compare of sham controls and as well the contralateral side of UL. However, on the 7th day after UL, this expression returned to basal levels. Furthermore, elevated mRNA and protein levels of H1, H2 and H3 receptors were observed in the ipsi-lesional MVN on the 1st day after UL compared with sham controls and as well the contralateral side of UL. However, this asymmetric expression was absent by the 3rd post-UL. Our findings suggest that the upregulation of histamine receptors in the MVN and the flocculus may contribute to rebalancing the spontaneous discharge in bilateral MVN neurons during vestibular compensation.