Molecular determinants of bat wing development

The specialization of the forelimb into a wing allowed bats to become the only mammals to achieve powered flight. Recent studies in developmental biology have begun to elucidate the molecular mechanisms behind elements of this important morphological transformation. Specifically, researchers have identified molecular changes contributing to: the formation of the bat wing membrane, the elongation of skeletal elements of the bat wing and the reduction of the bat ulna. The general picture emerging from this research is that small changes in the expression of genes critical to many aspects of development have driven large changes in bat wing morphology. Thus, bats can be added to the growing list of groups in which expression changes in key developmental genes have been linked to the evolution of morphological innovations (e.g. early bilaterians, cetaceans, insects).     

Bright light produces Fos-positive neurons in caudal trigeminal brainstem

Excessive discomfort after exposure to bright light often occurs after ocular injury and during headache. Although the trigeminal nerve is necessary for light-evoked discomfort, the mechanisms underlying this phenomenon, often referred to generally as photophobia, are not well defined. Quantitative Fos-like immunoreactivity (Fos-LI) was used to determine the pattern of neuronal activation in the caudal brainstem after bright light stimulation and, secondly, whether a neurovascular mechanism within the eye contributes to this response. Under barbiturate anesthesia, male rats were exposed to low (1×10⁴ lx) or high intensity (2×10⁴ lx) light delivered from a thermal neutral source for 30 min (30 s ON, 30 s OFF) and allowed to survive for 90 min. Intensity-dependent increases in Fos-LI were seen in laminae I–II at the trigeminal caudalis/cervical cord junction region (Vc/C1) and nucleus tractus solitarius (NTS). Fos-LI also increased at the trigeminal interpolaris/caudalis transition (Vi/Vc_vl) and dorsal paratrigeminal (dPa5) regions independent of intensity. Intravitreal injection of norepinephrine greatly reduced light-evoked Fos-LI at the Vc/C1, dPa5 and NTS, but not at the Vi/Vc transition. Lidocaine applied to the ocular surface had no effect on Fos-LI produced in trigeminal brainstem regions. These results suggested that multiple regions of the caudal trigeminal brainstem complex integrate light-related sensory information. Fos-LI produced at the dPa5 and NTS, coupled with norepinephrine-induced inhibition, was consistent with the hypothesis that light-evoked activation of trigeminal brainstem neurons involves an intraocular neurovascular mechanism with little contribution from neurons that supply the ocular surface.     

Diencephalic projections of the subnucleus interpolaris of the brainstem trigeminal complex in the rat

In this study the projection fields of the subnucleus interpolaris were examined using anterograde degeneration techniques. The projection areas of the subnucleus interpolaris in the diencephalon include the arcuate nucleus of the ventrobasal complex, the zona incerta, parts of the posterior nuclear group and the medial portions of the medial geniculate nucleus. Within the arcuate nucleus of the ventrobasal complex, the subnucleus interpolaris afferents are not uniform but, rather, clumped into islets. In addition, these projections exhibit a distinct topography with respect to the face representation in both the subnucleus interpolaris and the arcuate nucleus of the ventrobasal complex. The subnucleus interpolaris afferents convey approximately a 225° rotated map of the subnucleus interpolaris to the arcuate nucleus.The projection of the subnucleus interpolaris to the diencephalon is very similar to that of the principal sensory nucleus of the brainstem trigeminal complex (Smith, 1973). Implications of two separate systems relaying information from the face to the same areas in the diencephalon are discussed.     

50例正常人脑干三叉神经诱发电位分析

目的：探讨无伤害性刺激脑干三叉诱发电位(BTEP)的检测方法和波形特征。方法：对50名健康志愿者进行上唇电脉冲刺激,用远场记录法在头皮上记录刺激后10 ms内出现的反应波,寻找最适宜的刺激和记录参数。部分被试者同时进行脑干听觉诱发电位(BAEP)和正中神经短潜伏期体感诱发电位(SEP)检测。结果：50例正常人均记录到满意的BTEP反应波,其峰潜伏期、波间期值与文献资料近似。BTEP的脑干成分较BAEP和SSEP清晰、明确。结论：用无伤害刺激在正常人可以记录到清晰、稳定的BTEP反应波。BTEP为评价三叉神经周围结构和脑干中枢通路提供了新的、可靠的电生理学方法,是研究脑干功能的又一指标。     

The distribution of binding by isolectin I-B4 from Griffonia simplicifolia in the trigeminal ganglion and brainstem trigeminal nuclei in the rat.

The distribution of binding by the isolectin I-B4 from Griffonia simplicifolia in the rat trigeminal system has been investigated. This lectin binds to a sub-population of small-diameter trigeminal ganglion neurons. Double-labelling studies revealed that this lectin bound to all the trigeminal ganglion neurons containing somatostatin, whereas it bound to less than 25% of those containing calcitonin gene-related peptide or substance P. In the brainstem this lectin gave terminal-like staining in only the sub-nucleus caudalis of the trigeminal nuclei. In this nucleus, staining was most dense in the inner part of lamina II. Morphometric studies suggest that this lectin and that from the soybean recognize the same population of cells. The relationship of this data to those obtained in other studies using markers binding to glycoconjugates with a terminal alpha-galactose is discussed.     

Molecular determinants of exocytosis

Membrane fusion processes occur throughout the cell. Among those, exocytosis of secretory organelles is probably one of the fastest fusion events animal cells can achieve. Structural and functional studies have provided a conceptual framework and a starting point for our mechanistic understanding of how SNARE proteins may contribute to the final step in exocytosis.     

Identification of brainstem interneurons projecting to the trigeminal motor nucleus and adjacent structures in the rabbit

Neurons of several nuclei within the medial pontomedullar reticular formation are active during mastication, but their relationship with other elements of the pattern generating circuits have never been clearly defined. In this paper, we have studied the connection of this area with the trigeminal motor nucleus and with pools of last-order interneurons of the lateral brainstem. Retrograde tracing techniques were used in combination with immunohistochemistry to define populations of glutamatergic and GABAergic neurons. Injections of tracer into the Vth motor nucleus marked neurons in several trigeminal nuclei including the ipsilateral mesencephalic nucleus, the contralateral Vth motor nucleus, the dorsal cap of the main sensory nucleus and the rostral divisions of the spinal nucleus bilaterally. Many last-order interneurons formed a bilateral lateral band running caudally from Regio h (the zone surrounding the Vth motor nucleus), through the parvocellular reticular formation and Vth spinal caudal nucleus. Injections of tracer into Regio h, an area rich in last-order interneurons, marked, in addition to the areas listed above, a large number of neurons in the medial reticular formation bilaterally. The major difference between injection sites was that most neurons projecting to the Vth motor nucleus were located laterally, whereas most of those projecting to Regio h were found medially. Both populations contained glutamatergic and GABAergic neurons intermingled. Our results indicate that neurons of the medial reticular formation that are active during mastication influence Vth motoneurons output via relays in Regio h and other adjacent nuclei.     

A physiological study of brainstem and peripheral inputs to trigeminal motoneurons in lampreys

The inputs to trigeminal motoneurons from sensory afferents and rhombencephalic premotor regions were studied in isolated brainstem preparations of adult lampreys (Petromyzon marinus). Stimulation of both trigeminal nerves, contralateral nucleus motorius nervi trigemini, nucleus sensibilis nervi trigemini and ipsilateral rostral reticular formation elicited large-amplitude excitatory postsynaptic potentials with short latencies. These were significantly attenuated by adding 6-cyano-7-nitroquinoxaline2,3-dione (10 microM) and 2-amino-5-phosphonopentanoate (200 microM) to the bath, suggesting participation of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and N-methyl-D-aspartate receptors. The inputs from ipsilateral trigeminal afferents included a di- or oligosynaptic glycinergic inhibition. Sustained rhythmical membrane potential oscillations were observed in 52% of the recorded cells upon stimulation of trigeminal afferents or the contralateral nucleus sensibilis nervi trigemini. Two types of rhythm were obtained: (i) low-frequency oscillations (0.1-0.5 Hz), with peak-to-peak amplitudes between 8.5 and 17 mV; and (ii) higher frequency oscillations (1.0-2.8 Hz) with smaller amplitudes (1.8-5.1 mV). The two types of trigeminal rhythm could occur independently of fictive locomotion and fictive breathing. In a decerebrate semi-intact preparation, slow rhythmical trigeminal motoneuron potential oscillations were also evoked by stimulation of the oral disc. This study shows that trigeminal motoneurons receive excitatory synaptic inputs from several brainstem sites, and that membrane potential oscillations can be triggered upon stimulation of trigeminal afferents or the nucleus sensibilis nervi trigemini. We suggest that these oscillations recorded in vitro may represent the centrally generated components that underlie rhythmical feeding in lampreys.     

An anatomical study of brainstem projections to the trigeminal motor nucleus of lampreys.

This study was undertaken to identify and describe populations of brainstem neurons that project to the area of the nucleus motorius nervi trigemini in lampreys as a first step in the study of neurons that control feeding behavior in this species. To identify these neurons, the retrograde tracer cobalt-lysine was injected into the nucleus motorius nervi trigemini on one side of the in vitro isolated brainstem preparation of seven spawning adult lampreys (Petromyzon marinus). Transport times ranged from 42 to 48 h. Retrogradely labeled neurons were found within the rostral spinal cord, the rhombencephalon, the mesencephalon and the caudal diencephalon. This study concentrates on the labeled neurons in the rhombencephalon, since the essential circuits for mastication and swallowing are confined to this region in higher vertebrates. Within the rhombencephalon, labeled cells were in the nucleus sensibilis nervi trigemini on both sides. A densely packed column of labeled neurons was found medial to the nucleus motorius nervi trigemini on the ipsilateral side, extending further rostrally in the isthmic region. Continuous columns of labeled cells were observed in the lateral reticular formation on each side in the basal plate ventral to rhombencephalic cranial motor nuclei. They extended from the rostral trigeminal region down into the rostral spinal cord. A comparison with data from cats and rats shows that the distribution of neurons that project to the nucleus motorius nervi trigemini is very similar in mammals and in agnathes. We conclude that the organization of the motor command network of the trigeminal system is well preserved throughout phylogeny and that the in vitro isolated brainstem of lampreys should be a useful model for the study of vertebrate feeding behavior.     

Cannabinoid-induced presynaptic inhibition at the primary afferent trigeminal synapse of juvenile rat brainstem slices

Systemic or intraventricular administration of cannabinoids causes analgesic effects, but relatively little is known for their cellular mechanism. Using brainstem slices with the mandibular nerve attached, we examined the effect of cannabinoids on glutamatergic transmission in superficial trigeminal caudal nucleus of juvenile rats. The exogenous cannabinoid receptor agonist WIN 55,212-2 (WIN), as well as the endogenous agonist anandamide, hyperpolarized trigeminal caudal neurones and depressed the amplitude of excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) monosynaptically evoked by stimulating mandibular nerves in a concentration-dependent manner. The inhibitory action of WIN was blocked or fully reversed by the CB₁ receptor antagonist SR 141716A. WIN had no effect on the amplitude of miniature excitatory postsynaptic currents (mEPSCs) recorded in the presence of tetrodotoxin or cadmium. The inhibitory effect of WIN on EPSCs was greater for those with longer synaptic latency, suggesting that cannabinoids have a stronger effect on C-fibre EPSPs than on Aδ-fibre EPSPs. Ba²⁺ (100 μ m ) blocked the hyperpolarizing effect of cannabinoids, but did not affect their inhibitory effect on EPSPs. The N-type Ca²⁺ channel blocker ω-conotoxin GVIA (ω-CgTX) occluded the WIN-mediated presynaptic inhibition, whereas the P/Q-type Ca²⁺ channel blocker ω-agatoxin TK (ω-Aga) had no effect. These results suggest that cannabinoids preferentially activate CB₁ receptors at the nerve terminal of small-diameter primary afferent fibres. Upon activation, CB₁ receptors may selectively inhibit presynaptic N-type Ca²⁺ channels and exocytotic release machinery, thereby attenuating the transmitter release at the trigeminal nociceptive synapses.     

Molecular determinants of sterile inflammation

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Early development of the mesencephalic trigeminal nucleus.

The cells of the mesencephalic trigeminal nucleus (MTN) are the proprioceptive sensory neurons that innervate the jaw muscles. Interestingly, their evolution is generally thought to have been concomitant with that of the jaws. They are also the first born neurons of the mesencephalon, and their axons pioneer some of the major tracts within the brain. The cells of the MTN are also paradoxical in being the only group of intramedullary primary sensory neurons in amniotes. However, we know little about the early development of these important neurons, and we have analysed this here. To study the earliest stages of MTN development, we have used a battery of neural crest markers to try and pinpoint the progenitors of the MTN. We find that, contrary to current perceptions, the progenitors of the MTN are not highlighted by these markers, suggesting that they are not neural crest derived. However, the cells of the MTN are marked by means of their expression of Brn-3a. This gene labels cells that arise either side of the dorsal midline, extending rostrally from the isthmus across the roof of the mesencephalon. We have further demonstrated that the MTN develops under the influence of the Fgf-8 secreted by the isthmus. Ectopic Fgf-8 application promotes MTN development, whereas inhibiting Fgf-8 function in vivo drastically affects MTN development.     

Distribution of the low-affinity neurotrophin receptor (p75) in the developing trigeminal brainstem complex in the rat

The low-affinity neurotrophin receptor (p75) binds all members of the neurotrophin family. In the rat, during the first week postpartum, dense p75-immunoreactivity (IR) is present throughout all components of the trigeminal brainstem complex (TBC), largely associated with primary sensory afferents. Within subnucleus caudalis (SpC) of the TBC, intense p75-IR is present in all laminae at birth. During the second and third postnatal weeks, p75-IR in SpC gradually fades within the deeper laminae, becoming generally restricted in the adult to laminae I and II. Similar declines in p75-IR intensity occur in the subnucleus oralis (SpO); in the SpO in the adult, p75-IR is confined to the dorsalmost portion of SpO. In subnucleus interpolaris, an emerging, vibrissa-related pattern of p75-IR is detectable on PD0 (first 24 hr postpartum), which becomes fully differentiated during PD4-PD7. However, this pattern gradually disappears during the third postnatal week. Ventrally in the nucleus principalis (PrV), a pattern of p75-IR that mirrors the topographical arrangement of the vibrissae is detectable by PD0-PD1, is fully differentiated by the end of the first postnatal week, and persists into adulthood. Perinatal unilateral sectioning of the infraorbital nerve on PD0-PD1, but not as late as PD4, disrupts p75-IR patterning in the adult PrV. Although p75 appears to be associated with primary afferent pattern formation, to determine whether it is essential, we examined mutant mice unable to form functional p75. In the TBC of these knockout mice, examined as adults, patterns of cytochrome oxidase staining (which parallel those of p75-IR) appeared to be normal. In summary, during early development, p75 is widely expressed in the TBC during periods of active synaptogenesis and pattern formation, whereas in the adult, its expression is restricted to association with populations of primary sensory afferents. However, the absence of functional p75 in genetically altered mice does not appear to prevent primary afferent pattern formation.     

Anatomical landmarks for localizing the buccal branch of the trigeminal nerve on the face

The current literature is lacking in anatomical landmarks for identifying the buccal branch of the trigeminal nerve on the face. The current study was performed to elucidate this anatomy. Forty cadaveric sides underwent dissection to measure the distances from landmarks of the superficial face to the buccal nerve in this region. On average, the buccal nerve was found to lie 3 cm lateral to the angle of the mouth and at this same level, the nerve was located a mean of 5 mm medial to the medial aspect of the masseter muscle. The buccal nerve was found to be on average 7 mm from the point of entrance of the parotid duct into the buccinator muscle and had an average distance of 5.5 mm from the facial artery. We believe that additional landmarks for identifying the buccal nerve on the face may be of use to the surgeon and dentist.     

Peripheral development of avian trigeminal nerves

Development of the trigeminal nerve branches was studied in stage -17 to -27 chick embryos stained with an antibody to neurofilament protein. The following findings were obtained. (1) Ectopic ganglia transiently appeared in the ectoderm of the supraorbital region and were considered as remnant ophthalmic-placode-derived ganglia. (2) Most of the cutaneous sensory branches of the maxillomandibular nerve arose from a loosely arborized mass of neurites, provisionally termed the maxillomandibular reticulum, in which the fibers intermingled in a seemingly random fashion. (3) The growth of the trigeminal branches was mainly correlated with the development of the facial processes; however, irregular communications between different groups of branches were observed, suggesting that topographical organization of the peripheral branches is not rigid in early stages. (4) From the ophthalmic nerve around stage 23, transient dorsal rami developed and were distributed in the mesenchymal space, the cavum epiptericum, and passed near the ectoderm. Their homology with the rr. tentorii in human anatomy is suggested.