Brain stimulation-induced changes of phonation in the squirrel monkey

Summary In 11 squirrel monkeys (Saimiri sciureus), the brain stem was systematically explored with electrical brain stimulation for sites affecting the acoustic structure of ongoing vocalization. Vocalization was elicited by electrical stimulation of different brain structures. A severe deterioration of the acoustical structure of vocalization was obtained during stimulation of the caudoventral part of the periaqueductal grey, lateral parabrachial area, corticobulbar tract, nucl. ambiguus and surrounding reticular formation, facial nucleus, hypoglossal nucleus, solitary tract nucleus and along the fibres crossing the midline at the level of the hypoglossal nucleus. It is suggested that these structures are part of, or at least have direct access to, the motor coordination mechanism of phonation. Complete inhibition of phonation was obtained from the raphe and raphe-near reticular formation.Abbreviations Ab nucl ambiguus - APt area praetectalis - BC brachium conjunctivum - BP brachium pontis - Cb cerebellum - CC corpus callosum - Cd nucl. caudatus - Cf nucl. cuneiformis - Cel nucl. centralis lateralis - Cl claustrum - CM centrum medianum - Cn nucl. cuneatus - Co nucl. cochlearis - CoI colliculus inferior - CoS colliculus superior - CP commissura posterior - CPf cortex piriformis - CRf corpus restiforme - CSL nucl. centralis superior lateralis thalami - CT corpus trapezoideum - DBC decussatio brachii conjunctivi - DG nucl. dorsalis tegmenti (Gudden) - DLM decussatio lemnisci medialis - DPy decussatio pyramidum - DR nucl. dorsalis raphae - DV nucl. dorsalis n. vagi - DIV decussatio n. trochlearis - EP epiphysis - FC funiculus cuneatus - FL funiculus lateralis - FLM fasciculus longitudinalis medialis - FRM formatio reticularis myelencephali - FRP formatio reticularis pontis - FRPc formatio reticularis pontis caudalis - FRPo formatio reticularis pontis oralis - FRTM formatio reticularis mesencephali - FV funiculus ventralis - G nucl. gracilis - GC substantia grisea centralis (periaqueductal grey) - GL nucl. geniculatus lateralis - GM nucl. geniculatus medialis - GP globus pallidus - GPM griseum periventriculare mesencephali - GPo griseum pontis - Hip hippocampus - HL nucl. habenularis lateralis - H habenula - IP nucl. interpeduncularis - LC locus coeruleus - LD nucl. lateralis dorsalis thalami - Lim nucl. limitans - LLd nucl. lemnisci lateralis, pars dorsalis - LLv nucl. lemnisci lateralis, pars ventrali - LM lemniscus medialis - LP nucl. lateralis posterior thalami - MD nucl. medialis dorsalis thalami - MV nucl. motorius n. trigemini - NCS nucl. centralis superior - NCT nucl. trapezoidalis - NMV nucl. mesencephalicus n. trigemini - NR nucl. ruber - NSV nucl. spinalisn. trigemini - NTS nucl. tractus solitarii - NIII nucl. oculomotorius - NIV nucl. trochlearis - NVI nucl. abducens - NVII nucl. facialis - NXII nucl. hypoglossus - OI oliva inferior - OS oliva superior - P nucl. posterior thalami - PbL nucl. parabrachialis lateralis - PbM nucl. parabrachialis medialis - PC depedunculus cerebri - Pd nucl. peripeduncularis - Pg nucl. parabigeminalis - Pp nucl. praepositus - PuI nucl. pulvinaris inferior - PuL nucl. pulvinaris lateralis - PuM nucl. pulvinaris medialis - PuO nucl. pulvinaris oralis - Py tractus pyramidalis - Pv nucl. principalis n. trigemini - R Ab nucl. retroambiguus - RL nucl. reticularis lateralis - RTP nucl. reticularis tegmenti pontis - Sf nucl. subfascicularis - SGD substantia grisea dorsalis - SGV substantia grisea ventralis - SN substantia nigra - ST stria terminalis - St subthalamus - TRM tractus retroflexus (Meynert) - TSc tractus spinocerebellaris - Ves nucl. vestibularis - VL nucl. ventralis lateralis - VPI nucl. ventralis posterior inferior - VPL nucl. ventralis posterior lateralis - VPM nucl. ventralis posterior medialis - VR nucl. ventralis raphae - Zi zona incerta - II tractus opticus - VII n. facialis     

Afferent fiber connections from lower brain stem to hypothalamus studied by the horseradish peroxidase method with special reference to noradrenaline innervation

Summary Attempts were made to determine the afferent projections to the anterior hypothalamus including the preoptic area from the lower brain stem by means of the horseradish peroxidase method combined with monoamine oxidase staining to identify noradrenaline (NA) neurons. In addition to this technique, a histofluorescence analysis was performed. NA fibers in the medial part of the anterior hypothalamus were mainly supplied by A1 and A2 NA neuron groups, while the lateral part and periventricular zone received NA terminals from both pontine and medulla oblongata NA neuron groups. Furthermore, the present study indicated that there were direct projections to the anterior hypothalamus from non-noradrenergic neurons in the lower brain stem: nuclei raphe dorsalis, centralis superior, cells in the mesencephalic and pontine central gray matter, nuclei parabrachialis lateralis and medialis, cells around fasciculus longitudinalis medialis.Abbreviations CA Commissura anterior - CO Chiasma opticum - DP Decussatio pyramidum - DPCS Decussatio pedunculorum cerebellarium superiorum - F Columna fornicis - FLM Fasciculus longitudinalis medialis - FMT Fasciculus mamillothalamicus - GCM Griseum centrale mesencephali - GCP Griseum centrale pontis - LL Lemniscus lateralis - LM Lemniscus medialis - PCM Pedunculus cerebellaris medius - PCS Pedunculus cerebellaris superior - TO Tractus opticus - TS Tractus solitarius - TVme Tractus mesencephalicus nervi trigemini - V Ventriculus tertius - VTS Tractus spinalis nervi trigemini - am nucleus ambiguus - B Barrington nucleus - com nucleus commissuralis - cp nucleus caudatus putamen - cs nucleus centralis superior - ct nucleus corporis trapezoidei - cu nucleus cuneatus - dX nucleus dorsalis nervi vagi - Gd nucleus tegmentalis dorsalis (von Gudden) - gr nucleus gracilis - Gv nucleus tegmentalis ventralis (von Gudden) - ha nucleus hypothalamicus anterior - hl nucleus hypothalamicus lateralis - hpe nucleus periventricularis (hypothalami) - hvm nucleus ventromedialis hypothalami - lc nucleus locus coeruleus - oi nucleus olivaris inferior - p nucleus pontis - pa nucleus paraventricularis - pbl nucleus parabrachialis lateralis - pbm nucleus parabrachialis medialis - ph nucleus praepositus hypoglossi - pol nucleus preopticus lateralis - pom nucleus preopticus medialis - pop nucleus preopticus periventricularis - rd nucleus raphe dorsalis - re nucleus reuniens - rl nucleus reticularis lateralis - rm nucleus raphe magnus - ro nucleus raphe obscrus - sc nucleus suprachiasmaticus - so nucleus supraopticus - st nucleus interstitialis striae terminalis - td nucleus tractus diagonalis (Broca) - ts nucleus tractus solitarii - Vme nucleus mesencephalicus nervi trigemini - Vmo nucleus motorius nervi trigemini - Vts nucleus tractus spinalis nervi trigemini - XII nucleus nervi hypoglossi     

Histochemical mapping of succinic dehydrogenase and cytochrome oxidase in the pons and mesencephalon of squirrel monkey (Saimiri sciureus)

Summary The distribution of succinic dehydrogenase (SDA) and cytochrome oxidase (Cy. O) has been investigated in a series of sections through the pons and mesencephalon of the squirrel monkey brain. The localization of the two enzymes is very similar in the various regions and shows only slight differences. The epiphysis, however, shows moderately strong SDA and very mild Cy. O activity. Particularly strong SDA and Cy. O activity has been observed in the cell bodies of the various cranial nerve nuclei, nucleus colliculi inferioris, colliculi superioris, nuclei griseum pontis, reticularis tegmenti pontis, lemnisci lateralis pars dorsalis, geniculatum laterale and mediale, and pulvinaris. The enzyme content of the neurons and cell bodies is generally stronger compared to the neuropil which often occurs in smooth, loose, compact and reticulated forms. Any special relationship between the neurons and neuropil with regard to their enzyme content has, however, not been observed. The cranial nerves, and fibers of the brachium conjunctivum, corpus callosum, and fornix show very mild enzyme activity except those of the trapezoid complex which show moderate enzyme activity.Abbreviations Ann Nucleus annularis - APT Area praetectalis - AS Aquaeductus Sylvii - BC Brachium conjunctivum - BCI Brachium colliculi inferioris - BCS Brachium colliouli superioris - BP Brachium pontis - Cb Cerebellum - CC Corpus callosum - CCI Commissura colliculi inferioris - CCS Commissura colliculi superioris - Cd Nucleus caudatus - CHD Commissura hippocampi —parsdorsalis - CoI Colliculus inferior - CoP Commissura posterior - CoR Corona radiata - CoS Colliculus superior - CPf Cortex piriformis - CR Cortex retrosplenialis - DBC Decussatio brachii conjunctivi - DG Nucleus dorsalis tegmentalis(Gudden) - DR Nucleus dorsalis raphes - EP Epiphysis - F Fornix - FH Fimbria hippocampi - FLM Fasciculus longitudinalis medialis - FRPC Formatio reticularis pontis, parscaudalis - FRPO Formatio reticularis pontis, parsoralis - FRTM Formatio reticularis tegmentimesencephali - GC Substantia grisea centralis - GCd Substantia grisea centralis, parsdorsalis - GCv Substantia grisea centralis, parsventralis - GL Corpus geniculatum laterale - GM Corpus geniculatum mediate - GPO Griseum pontis - Hipp Hippocampus - HL Nucleus habenulae lateralis - HM Nucleus habenulae medialis - IP Nucleus interpeduncularis - LC Nucleus locus coeruleus - LCb Lingula cerebelli - Lim Nucleus limitans thalami - LL Lemniscus lateralis - LLD Nucleus lemnisci lateralis —parsdorsalis - LM Lemniscus medialis - LP Nucleus lateralis posterior thalami - MD Nucleus medialis dorsalis thalami - Mv Nucleus motorius n. trigemini - NCI Nucleus colliculi inferioris - NCS Nucleus centralis superior tegmenti - NCT Nucleus trapezoideum - NMv Nucleus tractus mesencephalicus n.trigemini - NR Nucleus ruber - NST Nucleus supratrochlearis - NSv Nucleus tractus spinalis n. trigemini - NiiiC Nucleus centralis n. oculomotorii - NiiiD Nucleus n. oculomotorii — pars dor-salis - NiiiV Nucleus n. oculomotorii — pars ven-tralis - Niv Nucleus n. troehlearis - nvm Nervus trigeminus, portio major - niv Nervus trochlearis - nvi Nervus abducens - OS Nucleus olivaris superior - P Nucleus posterior thalami - PbL Nucleus parabrachialis lateralis - PbM Nucleus parabrachialis medialis - PC Pedunculus cerebri - Pg Nucleus parabigeminalis - PUI Nucleus pulvinaris inferior thalami - PUL Nucleus pulvinaris lateralis thalami - PUM Nucleus pulvinaris medialis thalami - Py Tractus pyramidalis - Pv Nucleus principalis n. trigemini - R Nucleus reticularis thalami - RTP Nucleus reticularis tegmenti pontis - SNc Substantia nigra — pars compacta - SNd Substantia nigra — pars diffusa - Sub Subiculum - TCT Tractus corticotectalis - VR Nucleus ventralis raphes - III Ventriculus tertius - IV Ventriculus quartus     

Origin and fine structure of substance P-containing nerve terminals in the facial nucleus of the rat: an immunohistochemical study

Summary The distribution, origin and fine structure of substance P-like immunoreactive (SPI) nerve terminals in the facial nucleus of the rat were investigated by means of immunocytochemistry. SPI-terminals were concentrated in the intermediate and dorsal subnuclei of the facial nucleus. Hemi-transection of the brainstem just rostral to the facial nucleus or at the most caudal level of the medulla oblongata did not cause any change of SPI-terminals in the facial nucleus. Electrical destruction of the various parts of the medulla oblongata clearly demonstrated that SPI-terminals in the intermediate subnucleus were supplied contralaterally from the SPI-neurons in the dorsomedial part of the medullary reticular formation. Most of the SPI-terminals (85%) in the intermediate subnucleus of the facial nucleus were observed to make asymmetric synaptic contacts with large dendrites (mean diameter; 1.26 m). It was supposed that the contact sites are located on proximal parts of the dendrite. A few SPI-terminals (6%) formed axo-somatic contacts with large perikarya filled with numerous cytoplasmic organelles.Abbreviations used in Figures A n. ambiguus - AP area postrema - C n. cuneatus - Cod n. cochlearis dorsalis - Cov n. cochlearis ventralis - CU n. cuneiformis - FLM fasciculus longitudinalis medialis - G n. gracilis - MRF midbrain reticular formation - nts n. tractus solitarius - nVsp n. tractus spinalis nervi trigemini - nVII n. originis nervi facialis - nX n. originis dorsalis vagi - nXII n. originis nervi hypoglossi - OI n. olivaris inferior - rfl the ventro-lateral part of the caudal medullary reticular formation - rfm the dorso-medial part of the medullary reticular formation - RL n. reticularis lateralis - RM n. raphe magnus - rmg n. reticularis magnocellularis - RO n. raphe obscurus - sgc substantia grisea centralis - Vl n. vestibularis lateralis - Vm n. vestibularis medialis - Vsp n. vestibularis spinalis     

Nuclear organization of some immunohistochemically identifiable neural systems in two species of the Euarchontoglires: A Lagomorph,Lepus capensis,and a Scandentia,Tupaia belangeri

The present study describes the organization of the nuclei of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of two members of Euarchontoglires, Lepus capensis and Tupaia belangeri. The aim of the present study was to investigate the nuclear complement of these neural systems in comparison to previous studies on Euarchontoglires and generally with other mammalian species. Brains were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei revealed in the current study were similar between the species investigated and to mammals generally, but certain differences in the nuclear complement highlight potential phylogenetic interrelationships within the Euarchontoglires and across mammals. In the northern tree shrew the nucleus of the trapezoid body contained neurons immunoreactive to the choline acetyltransferase antibody with some of these neurons extending into the lamellae within the superior olivary nuclear complex (SON). The cholinergic nature of the neurons of this nucleus, and the extension of cholinergic neurons into the SON, has not been noted in any mammal studied to date. In addition, cholinergic neurons forming the medullary tegmental field were also present in the northern tree shrew. Regarding the catecholaminergic system, the cape hare presented with the rodent specific rostral dorsal midline medullary nucleus (C3), and the northern tree shrew lacked both the ventral and dorsal divisions of the anterior hypothalamic group (A15v and A15d). Both species were lacking the primate/megachiropteran specific compact portion of the locus coeruleus complex (A6c). The nuclei of the serotonergic and orexinergic systems of both species were similar to those seen across most Eutherian mammals. Our results lend support to the monophyly of the Glires, and more broadly suggest that the megachiropterans are more closely related to the primates than are any other members of Euarchontoglires studied to date.     

Vocalization-correlated single-unit activity in the brain stem of the squirrel monkey

Summary The brain stems of 17 squirrel monkeys (Saimiri sciureus) were systematically explored for vocalization-related single-unit activity during calls electrically elicited from the periaqueductal grey. Of 12,280 cells tested, 1151 fired in relation to vocalization. Of these, 587 reacted to external acoustic stimuli and started firing after vocalization onset. As most of these cells were located in classical auditory relay structures, they probably represent auditory neurones reacting indirectly to self-produced vocalization due to auditory feedback. Seven cells reacted to acoustic stimuli but fired in advance of self-produced vocalization. These cells were locoated in the pericentral inferior colliculus, dorsal nucleus of the lateral lemniscus, dorsomedial to the ventral nucleus of the lateral lemniscus and immediately lateral to the central grey. They are probably engaged in tuning the auditory system to process self-generated sounds differently from external sounds. 261 neurones reacted to nonphonatory oral movements (chewing, swallowing) and started firing after vocalization onset. These neurones were widely distributed within the brain stem, with the highest density in the spinal trigeminal nucleus and medially adjacent reticular formation. The majority of these cells seem to react to proprioceptive and tactile stimuli generated by phonatory and nonphonatory oral activities. Some of them may exert motor control on muscles that come into play at later stages of phonation. 57 neurones reacted to nonphonatory oral movements but fired in advance of vocalization onset. These neurones were located mainly in the trigeminal motor nucleus, nucl. ambiguus, reticular formation around these nuclei, parabrachial region and lateral vestibular nucleus. Their role in motor control seems to be related to specific muscles rather than specific functions. 100 of the vocalization-related cells showed a correlation with respiration. Expiration-related cells were found in and around the rostral nucl. ambiguus and in the reticular formation dorsal to the facial nucleus. Inspiration-related cells were located in the rostral and caudal nucl. ambiguus regions, ventrolateral solitary tract nucleus and the lateral reticular formation below the trigeminal motor nucleus. Most of these cells probably represent premotor neurones of respiratory muscles and laryngeal motoneurones of the cricothyroid and posterior cricoarytenoid muscles. Finally, a last group of cells was found that was unresponsive to chewing and swallowing movements, quiet breathing and acoustic stimuli, but changed activity during vocalization. 38 of them became active before vocalization and cricothyroid activity, and 101 afterward. Both types were completely intermingled and scattered widely in the brain stem, including the nucl. ambiguus region, solitary tract nucleus, nucl. reticularis parvocellularis and gigantocellularis, parabrachial region, pericentral colliculus inferior, vestibular complex, periventricular grey and laterally adjacent tegmentum. Some of these cells may be related to vocalization in a more specific way.Abbreviations A nucl. annularis - Ab nucl. ambiguus - Apt area praetectalis - BC brachium conjunctivum - BP brachium pontis - Cb cerebellum - CC corpus callosum - Cd nucl. caudatus - Col colliculus inferior - CoS colliculus superior - CRf corpus restiforme - DBC decussatio brachii conjunctivi - DG nucl. dorsalis tegmenti (Gudden) - DR nucl. dorsalis raphae - DV nucl. ventralis n. vagi - FRM formatio reticularis myelencephali - FRP formatio reticularis pontis - FRTM formatio reticularis mesencephali - GC substantia grisea centralis - GL corpus geniculatum laterale - GM corpus geniculatum mediale - GPM griseum periventriculare mesencephali - GPo griseum pontis - H habenula - Hip hippocampus - IP nucl. interpeduncularis - LC locus coeruleus - LL lemniscus lateralis - LLd nucl. dorsalis lemnisci lateralis - LLv nucl. ventralis lemnisci lateralis - LM lemniscus medialis - LP nucl. lateralis posterior thalami - MD nucl. medialis dorsalis thalami - MV nucl. motorius n. trigemini - NC nucl. cochlearis - NCb nucl. cerebelli - NCS nucl. centralis superior - NCT nucl. trapezoidalis - NR nucl. ruber - NST nucl. supratrochlearis - NSV nucl. spinalis n. trigemini - NTS nucl. tractus solitarii - NIII nucl. oculomotorius - NIV nucl. trochlearis - nV nervus trigeminus - NVI nucl. abducens - NVII nucl. facialis - NXII nucl. hypoglossus - OI oliva inferior - PbL nucl. parabrachialis lateralis - PbM nucl. parabrachialis medialis - Pp nucl. praepositus - Pu nucl. pulvinaris oralis - PuL nucl. pulvinaris lateralis - PuM nucl. pulvinaris medialis - Py tractus pyramidalis - PV nucl. principalis n. trigemini - RL nucl. reticularis lateralis - RTP nucl. reticularis tegmenti pontis - SN substantia nigra - ST stria terminalis - Ves nucl. vestibulares - VR nucl. ventralis raphae - IV decussatio n. trochlearis Supported by Deutsche Forschungsgemeinchaft grant Ju 181/1     

Nuclear organization of cholinergic,catecholaminergic, serotonergic and orexinergic systems in the brain of the Tasmanian devil (Sarcophilus harrisii)

This study investigated the nuclear organization of four immunohistochemically identifiable neural systems (cholinergic, catecholaminergic, serotonergic and orexinergic) within the brains of three male Tasmanian devils (Sarcophilus harrisii), which had a mean brain mass of 11.6 g. We found that the nuclei generally observed for these systems in other mammalian brains were present in the brain of the Tasmanian devil. Despite this, specific differences in the nuclear organization of the cholinergic, catecholaminergic and serotonergic systems appear to carry a phylogenetic signal. In the cholinergic system, only the dorsal hypothalamic cholinergic nucleus could be observed, while an extra dorsal subdivision of the laterodorsal tegmental nucleus and cholinergic neurons within the gelatinous layer of the caudal spinal trigeminal nucleus were observed. Within the catecholaminergic system the A4 nucleus of the locus coeruleus complex was absent, as was the caudal ventrolateral serotonergic group of the serotonergic system. The organization of the orexinergic system was similar to that seen in many mammals previously studied. Overall, while showing strong similarities to the organization of these systems in other mammals, the specific differences observed in the Tasmanian devil reveal either order specific, or class specific, features of these systems. Further studies will reveal the extent of change in the nuclear organization of these systems in marsupials and how these potential changes may affect functionality.     

Projections from the rat cuneiform nucleus to the A7, A6 (locus coeruleus), and A5 pontine noradrenergic cell groups

Stimulation of neurons in the cuneiform nucleus (CnF) produces antinociception and cardiovascular responses that could be mediated, in part, by noradrenergic neurons that innervate the spinal cord dorsal horn. The present study determined the projections of neurons in the CnF to the pontine noradrenergic neurons in the A5, A6 (locus coeruleus), and A7 cell groups that are known to project to the spinal cord. Injections of the anterograde tracer, biotinylated dextran amine in the CnF of Sasco Sprague-Dawley rats labeled axons located near noradrenergic neurons that were visualized by processing tissue sections for tyrosine hydroxylase-immunoreactivity. Anterogradely labeled axons were more dense on the side ipsilateral to the BDA deposit. Both A7 and A5 cell groups received dense projections from neurons in the CnF, whereas locus coeruleus received only a sparse projection. Highly varicose anterogradely labeled axons from the CnF were found in close apposition to dendrites and somata of tyrosine hydroxylase-immunoreactive neurons in pontine tegmentum. Although definitive evidence for direct pathways from CnF neurons to the pontine noradrenergic cell groups requires ultrastructural analysis, the results of the present studies provide presumptive evidence of direct projections from neurons in the CnF to the pontine noradrenergic neurons of the A7, locus coeruleus, and A5 cell groups. These results support the suggestion that the analgesia and cardiovascular responses produced by stimulation of neurons in the CnF may be mediated, in part, by pontine noradrenergic neurons.     

Effect of low estrogen on neurons in the preoptic area of hypothalamus of ovariectomized rats

The purpose of this study was to investigate the difference in neuronal activity in the preoptic area of the hypothalamus (POAH) under low estrogen condition induced by ovariectomy. One hundred and twenty sham-operated (SHAM) and ovariectomized (OVX) rats were placed in different temperatures for 2 h. Twelve rats from each group were stimulated by 4 °C, 10 °C, 25 °C, 33 °C and 38 °C, respectively. c-Fos expression in the POAH was detected by immunohistochemistry. Following exposure to warm and cold stimuli, there were markedly lower c-Fos-positive cell densities in the OVX group compared with the SHAM group in the median preoptic nucleus (MnPO) at 4 °C, 10 °C, 33 °C and 38 °C, in the medial preoptic area (MPA) at 25 °C and 38 °C, in the ventromedial preoptic nucleus (VMPO) at 4 °C, 10 °C and 38 °C and in the ventrolateral preoptic nucleus (VLPO) at 4 °C and 38 °C. Both temperature and surgery had an impact on c-Fos expression by two-way ANOVA method except in the lateral preoptic area (LPO). c-Fos expression differed within different nuclei of the two groups in the same and different temperature stimuli. This indicated that the temperature-sensitive nuclei in the POAH exhibited lower and different activities during temperature stimuli following ovariectomy, which possibly resulted in abnormal thermoregulation and menopausal symptoms.     

The centrally projecting Edinger–Westphal nucleus—I: Efferents in the rat brain

The oculomotor accessory nucleus, often referred to as the Edinger–Westphal nucleus [EW], was first identified in the 17th century. Although its most well known function is the control of pupil diameter, some controversy has arisen regarding the exact location of these preganglionic neurons. Currently, the EW is thought to consist of two different parts. The first part [termed the preganglionic EW—EWpg], which controls lens accommodation, choroidal blood flow and pupillary constriction, primarily consists of cholinergic cells that project to the ciliary ganglion. The second part [termed the centrally projecting EW—EWcp], which is involved in non-ocular functions such as feeding behavior, stress responses, addiction and pain, consists of peptidergic neurons that project to the brainstem, the spinal cord and prosencephalic regions. However, in the literature, we found few reports related to either ascending or descending projections from the EWcp that are compatible with its currently described functions. Therefore, the objective of the present study was to systematically investigate the ascending and descending projections of the EW in the rat brain. We injected the anterograde tracer biotinylated dextran amine into the EW or the retrograde tracer cholera toxin subunit B into multiple EW targets as controls. Additionally, we investigated the potential EW-mediated innervation of neuronal populations with known neurochemical signatures, such as melanin-concentrating hormone in the lateral hypothalamic area [LHA] and corticotropin-releasing factor in the central nucleus of the amygdala [CeM]. We observed anterogradely labeled fibers in the LHA, the reuniens thalamic nucleus, the oval part of the bed nucleus of the stria terminalis, the medial part of the central nucleus of the amygdala, and the zona incerta. We confirmed our EW–LHA and EW–CeM connections using retrograde tracers. We also observed moderate EW-mediated innervation of the paraventricular nucleus of the hypothalamus and the posterior hypothalamus. Our findings provide anatomical bases for previously unrecognized roles of the EW in the modulation of several physiologic systems.     

The vestibulothalamic projections in the cat studied by retrograde axonal transport of horseradish peroxidase

Summary Horseradish peroxidase (HRP) was injected or iontophoretically ejected in various thalamic nuclei in 63 adult cats. In 11 other animals HRP was deposited outside the thalamic territory. The number and distribution of labelled cells within the vestibular nuclear complex (VC) were mapped in each case. To a varying degree all subgroups of VC appear to contribute to the vestibulothalamic projections. Such fibres are distributed to several thalamic areas. From the present investigation it appears that generally speaking, there exist three distinct vestibulothalamic pathways with regard to origin as well as to site of termination of the fibres. One projection appears to originate mainly in caudal parts of the medial (M) and descending (D) vestibular nuclei and in cell group z. This pathway terminates chiefly in the contralateral medial part of the posterior nucleus of the thalamus (POm) including the magnocellular part of the medial geniculate body (Mgmc), the ventrobasal complex (VB) and the area of the ventral lateral nucleus (VL) bordering on VB. A second projection originates mainly in the superior vestibular nucleus (S) and in cell group y and terminates mainly in the contralateral nucleus centralis lateralis (CL) and the adjoining nucleus paracentralis (Pc). A third, more modest, pathway originates chiefly in the middle M and D, with a minor contribution from S and cell group y, and terminates in the contralateral ventral nucleus of the lateral geniculate body (GLV). There is some degree of overlap between the origin of these three vestibulothalamic pathways.Abbreviations B.c. brachium conjunctivum - CeM nucleus centralis medialis thalami - CL nucleus centralis lateralis thalami - CM nucleus centrum medianum - D nucleus vestibularis descendons - f cell group f - g cell group g - GLD corpus geniculatum laterale dorsalis - GLV corpus geniculatum laterale ventralis - i.e. nucleus intercalatus - L nucleus vestibularis lateralis - LD nucleus lateralis dorsalis thalami - LIM lamina medullaris interna - Lim nucleus limitans - LP nucleus lateralis posterior thalami - M nucleus vestibularis medialis - MD nucleus medialis dorsalis thalami - MGmc corpus geniculatum mediale, pars magnocellularis - MGp corpus geniculatum mediale, pars principalis - N.cu.e. nucleus cuneatus externus - N.f.c. nucleus fasciculi cuneati - N.mes. V nucleus mesencephalicus nervi trigemini - NR nucleus ruber - N.tr.s. nucleus tractus solitarius - N. VII nervus facialis - N. VIII nervus statoacusticus - PC pedunculus cerebri - Pc nucleus paracentralis thalami - Pf nucleus parafascicularis - p.h. nucleus prepositus hypoglossi - PO posterior thalamic group - PO1 lateral part of PO - POm medial part of PO - Prt nucleus pretectalis - Pul pulvinar - R nucleus reticularis thalami - S nucleus vestibularis superior - Sg nucleus suprageniculatus - SN substantia nigra - Sv nucleus supravestibularis - Tr.s. tractus solitarius - VA nucleus ventralis anterior thalami - VL nucleus ventralis lateralis thalami - VPL nucleus ventralis posterior lateralis - VPL1 lateral part of VPL - VPLm medial part of VPL - VPM nucleus ventralis posterior medialis - x cell group x - y cell group y - z cell group z - V nucleus motorius nerve trigemini - X nucleus dorsalis nerve vagi - XII nucleus nervi hypoglossi     

Orexinergic innervation of urocortin1 and cocaine and amphetamine regulated transcript neurons in the midbrain centrally projecting Edinger–Westphal nucleus

Orexin is a neuropeptide that has been implicated in several processes, such as induction of appetite, arousal and alertness and sleep/wake regulation. Multiple lines of evidence also suggest that orexin is involved in the stress response. When orexin is administered intracerebroventricular it activates the hypothalamic pituitary adrenal (HPA)-axis, which is the main regulator of the stress response. The HPA-axis is not the only player in the stress response evidence suggests that urocortin 1 (Ucn1), a member of the corticotropin releasing factor (CRF) neuropeptide family, also plays an important role in the stress response adaptation. Ucn1 is primarily synthetized in the centrally projecting Edinger–Westphal nucleus (EWcp), which also receives dense innervation by orexin terminals. In this study we tested the hypothesis that orexin would directly shape the response of EWcp-Ucn1 neurons to acute cold stress. To test this hypothesis, we first assessed whether orexinergic axon terminals would innervate EWcp-Ucn1/CART neurons, and next we exposed orexin deficient (orexin-KO) male mice and their male wild-type (WT) littermates to acute cold stress for 2 h. We also assessed stress-associated changes in plasma corticosterone (CORT), as well as the activation of Ucn1/CART neurons in the EWcp nucleus. We found that orexin immunoreactive axon terminals were juxtaposed to EWcp-Ucn1/CART neurons, which also expressed orexin receptor 1 mRNA. Furthermore, acute stress strongly activated the EWcp-Ucn1/CART neurons and increased plasma CORT in both WT littermates and orexin-KO mice, however no genotype effect was found on these indices. Taken together our data show that orexin in general is not involved in the animal's acute stress response (plasma CORT) and it does not play a direct role in shaping the response of EWcp-Ucn1 neurons to acute stress either.     

Localization of Na+–K+-ATPase α/β, Na+–K+–2Cl-cotransporter 1 and aquaporin-5 in human eccrine sweat glands

In order to evaluate the function of the repaired or regenerated eccrine sweat glands, we must first localize the proteins involved in sweat secretion and absorption in normal human eccrine sweat glands. In our studies, the cellular localization of Na⁺–K⁺-ATPase α/β, Na⁺–K⁺–2Cl-cotransporter 1 (NKCC1) and aquaporin-5 (AQP5) in eccrine sweat glands were detected by immunoperoxidase labeling. The results showed that Na⁺–K⁺-ATPase α was immunolocalized in the cell membrane of the basal layer and suprabasal layer cells of the epidermis, the basolateral membrane of the secretory coils, and the cell membrane of the outer cells and the basolateral membrane of the luminal cells of the ducts. The localization of Na⁺–K⁺-ATPase β in the secretory coils was the same as Na⁺–K⁺-ATPase α, but Na⁺–K⁺-ATPase β labeling was absent in the straight ducts and epidermis. NKCC1 labeling was seen only in the basolateral membrane of the secretory coils. AQP5 was strongly localized in the apical membrane and weakly localized in the cytoplasm of secretory epithelial cells. The different distribution of these proteins in eccrine sweat glands was related to their functions in sweat secretion and absorption.     

Myelin repair in vivo is increased by targeting oligodendrocyte precursor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF)

Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system (CNS). Many nerve axons are insulated by a myelin sheath and their demyelination not only prevents saltatory electrical signal conduction along the axons but also removes their metabolic support leading to irreversible neurodegeneration, which currently is untreatable. There is much interest in potential therapeutics that promote remyelination and here we explore use of leukaemia inhibitory factor (LIF), a cytokine known to play a key regulatory role in self-tolerant immunity and recently identified as a pro-myelination factor. In this study, we tested a nanoparticle-based strategy for targeted delivery of LIF to oligodendrocyte precursor cells (OPC) to promote their differentiation into mature oligodendrocytes able to repair myelin. Poly(lactic-co-glycolic acid)-based nanoparticles of ∼120 nm diameter were constructed with LIF as cargo (LIF-NP) with surface antibodies against NG-2 chondroitin sulfate proteoglycan, expressed on OPC. In vitro, NG2-targeted LIF-NP bound to OPCs, activated pSTAT-3 signalling and induced OPC differentiation into mature oligodendrocytes. In vivo, using a model of focal CNS demyelination, we show that NG2-targeted LIF-NP increased myelin repair, both at the level of increased number of myelinated axons, and increased thickness of myelin per axon. Potency was high: a single NP dose delivering picomolar quantities of LIF is sufficient to increase remyelination.Impact statementNanotherapy-based delivery of leukaemia inhibitory factor (LIF) directly to OPCs proved to be highly potent in promoting myelin repair in vivo: this delivery strategy introduces a novel approach to delivering drugs or biologics targeted to myelin repair in diseases such as MS.     

Efferent fiber projections of the habenula and the interpeduncular nucleus. An experimental study in the opossum and cat

Summary A study of efferent fiber connections of the habenula and the inter-peduncular nucleus was conducted using anterograde degeneration techniques. Lesions were placed in the habenula of the opossum and the habenula and interpeduncular nucleus of the cat. Degeneration was studied by means of the Nauta and Fink-Heimer techniques.Fibers from the habenular nucleus of the opossum extended caudally and were traced bilaterally to the interpeduncular nucleus, dorsal tegmental nucleus of Gudden, deep (ventral) tegmental nucleus of Gudden, nucleus centralis superior and nucleus reticularis tegmenti pontis. Rostrally fibers were traced to the preoptic and septal region and the anterior and lateral hypothalamus.The medial and lateral habenular nuclei of the cat projected differentially to portions of the interpeduncular nucleus and the tegmental nuclei of Gudden. The medial habenular nucleus sent fibers to the paramedian subnucleus of the interpeduncular nucleus and to the deep tegmental nucleus; whereas the lateral habenular nucleus distributed to the apical and central subnuclei of the interpeduncular nucleus and the dorsal tegmental nucleus.Fibers from both the medial and lateral habenular nuclei were found to project bilaterally to the nucleus paraventricularis anterior, nucleus ventralis anterior, anterior medialis and anterior dorsalis of the thalamus, and the septal area.Fibers from the interpeduncular nucleus of the cat were represented bilaterally. Those passing rostral went to the lateral habenular nucleus, nucleus centromedianus and parafascicularis of the thalamus, and to the septal area. Those directed caudally projected to the nucleus centralis superior, and the dorsal and deep tegmental nucleus of Gudden.Abbreviations AC anterior commissure - AD nucleus anterior dorsalis - AM nucleus anterior medialis - AV nucleus anterior ventralis - BC brachium conjunctivum - CC corpus callosum - CD caudate nucleus - CI internal capsule - CL nucleus centralis lateralis - CM nucleus centromedianus - CP cerebral peduncle - DT dorsal tegmental nucleus (of Gudden) - EN entopeduncular nucleus - Fx fornix - GC central gray - GL lateral geniculate nucleus - GM medial geniculate nucleus - GP globus pallidus - HbPt habenulopeduncular tract - HVM ventromedial hypothalamic nucleus - IC inferior colliculus - IP interpeduncular nucleus - LHb lateral habenular nucleus - LL lateral lemniscus - LMN lateral mammillary nucleus - LP nucleus lateralis posterior - MD nucleus medialis dorsalis - MHb medial habenular nucleus - ML medial lemniscus - MMN medial mammillary nucleus - MP mammillary peduncle - NCM nucleus centralis medialis - OC optic chiasm - OT optic tract - Pf nucleus parafascicularis - Pul pulvinar - PUT putamen - RE nucleus reuniens - RN red nucleus - RPO preoptic area - RTP nucleus reticularis tegmenti pontisv (von Bechterew) - S stria medullaris - SC superior colliculus - SN substantia nigra - SPT septal area - VA nucleus ventralis anterior - VL nucleus ventralis lateralis - VM nucleus ventralis medialis - VPL nucleus ventralis posterolateralis - VPM nucleus ventralis posteromedialis - VT deep tegmental nucleus (of Gudden) - II optic nerve     

Distribution of serotonin-immunoreactivity in the brain of the pigeon (Columba livia)

The distribution of serotonin (5-HT)-containing perikarya, fibers and terminals in the brain of the pigeon (Columba livia) was investigated, using immunohistochemical and immunofluorescence methods combined with retrograde axonal transport. Twenty-one different groups of 5-HT immunoreactive (IR) cells were identified, 2 of which were localized at the hypothalamic level (periventricular organ, infundibular recess) and 19 at the tegmental-mesencephalic and rhombencephalic levels. Ten of the cell groups were situated within the region of the midline from the isthmic to the posterior rhombencephalic level and constituted the raphe system (nucleus annularis, decussatio brachium conjunctivum, area ventralis, external border of the nucleus interpeduncularis, zona peri-nervus oculomotorius, zona perifasciculus longitudinalis medialis, zona inter-flm, nucleus linearis caudalis, nucleus raphe superior pars ventralis, nucleus raphe inferior). The 9 other cell populations belonged to the lateral group and extended from the posterior mesencephalic tegmentum to the caudal rhombencephalon [formatio reticularis mesencephali, nucleus ventrolateralis tegmenti, ectopic area (Ec) of the nucleus isthmo-opticus (NIO), nucleus subceruleus, nucleus ceruleus, nucleus reticularis pontis caudalis, nucleus vestibularis medialis, nucleus reticularis parvocellularis and nucleus reticularis magnocellularis]. Combining the retrograde axonal transport of rhodamine -isothiocyanate (RITC) after intraocular injection and immunohistofluorescence (fluoresceine isothiocyanate: FITC/5-HT) showed the centrifugal neurons (NIO, ec) to be immunonegative. Serotonin-IR fibers and terminals were found to be very broadly distributed within the brain and were particularly prominent in several structures of the telencephalon (archistriatum pars dorsalis, nucleus taeniae, area parahippocampalis, septum), diencephalon (nuclei preopticus medianus, magnocellularis, nucleus geniculatus lateralis pars ventralis, nucleus triangularis, nucleus pretectalis), mesencephalon-rhombencephalon (superficial layers of the optic tectum, nucleus ectomamillaris, nucleus isthmo-opticus and in most of the cranial nerve nuclei). Comparing the present results with those of previous studies in birds suggests some major serotonin containing pathways in the avian brain and clarifies the possible origin of the serotonin innervation of some parts of the brain. Moreover, comparing our results in birds with those obtained in other vertebrate species shows that the organization of the serotoninergic system in many regions of the avian brain is much like that found in reptiles and mammals.Abbreviations Ad Archistriatum pars dorsalis - alp area interpeduncularis - al ansa lenticularis - Ann nucleus annularis - APH area parahippocampalis - Av archistriatum pars ventralis - AVT area ventralis (Tsai) - bcd brachium conjunctivum descendens - BO bulbus olfactorius - ca commisssura anterior - CDL area corticoidea dorsolateralis - Cer cerebellum - cf fiber layer of the olfactory bulb - cg granular cell layer of the olfactory bulb - co chiasma opticum - ct commissura tectalis - dbc decussatio brachiorum conjunctivorum - DL nucleus dorsolateralis anterior thalami - DLP nucleus dorsolateralis posterior thalami - DM nucleus dorsomedialis thalami - dnt decussatio nervi trochlearis - E ectostriatum - Ec ectopic area of the nucleus isthmo-opticus - EM nucleus ectomamillaris - flm fasciculus longitudinalis medialis - fpl fasciculus prosencephali lateralis - FRL formatio reticularis lateralis mesencephali - FRM formatio reticularis medialis mesencephali - fu fasciculus uncinatus - GCt substantia grisea centralis - GLv nucleus geniculatus lateralis pars ventralis - gr granular cell layer of the cerebellum - HA hyperstriatum accessorium - HD hyperstriatum dorsale - HIS hyperstriatum intercalatus superior - HL nucleus habenularis lateralis - HM nucleus habenularis medialis - Hp hippocampus - HV hyperstriatum ventrale - ICo nucleus intercollicularis - i-flm inter fasciculus longitudinalis medialis - Imc nucleus ishmi pars magnocellularis - Ip nucleus interpeduncularis - Ipc nucleus isthmi pars parvocellularis - LA nucleus lateralis anterior thalami - La nucleus laminaris - LC nucleus linearis caudalis - LHy nucleus lateralis hypothalami - lm lemniscus medialis - LoC locus coeruleus - LPO lobus paraolfactorius - ls lemniscus spinalis - MLd nucleus mesencephalicus lateralis pars dorsalis - mo molecular layer of the cerebellum - MoV nucleus motorius nervi trigemini - Mp magnocellularis preopticus - N neostriatum - NIII nucleus nervi oculomotorii - nIII nervus oculomotorius - NIV nucleus nervi trochlearis - NV nucleus nervi trigemini nV nervus trigeminus - NVII nucleus nervifacialis - nVIII nervus octavus - NIO nucleus isthmo-opticus - om tractus occipitomesencephalicus - OPH hypothalamic periventricular organ - Os nucleus olivaris superior - Ov nucleus ovoidalis - PA paleostriatum augmentatum - Po nucleus pontis - POM nucleus preoticus medialis - PP paleostriatum primitivum - PrV nucleus sensorius principalis nervi trigemini - PT nucleus pretectalis - pu Purkinje cell layer - qf tractus quintofrontalis - Rai nucleus raphe inferior - RasV nucleus raphe superior pars ventralis - ReI recessus infundibularis - Rm nucleus reticularis magnocellularis - Rp nucleus reticularis parvocellularis - RPc nucleus reticularis pontis caudalis - RPO nucleus reticularis pontis oralis - Rt nucleus rotundus - Ru nucleus ruber - S septum - Sac stratum album centrale - SCH stratum cellulare hypothalami - Sgc stratum griseum centrale - Sgf stratum griseum et fibrosum superficiale - Sgfp stratum griseum et fibrosum periventriculare - Sop stratum opticum - SP nucleus subpretectalis - SPC nucleus superficialis parvocellularis - Spl nucleus spiriformis lateralis - Spm nucleus spiriformis medialis - SRt nucleus subrotundus - SuC nucleus subcoeruleus - to tractus opticus - Tn nucleus taeniae - TPc nucleus tegmenti pedunculo-pontinus pars compacta - Tr nucleus triangularis - tsm tractus septomesencephalicus - ttd nucleus et tractus descendens nervi trigemini - Tu nucleus tuberis - Vel nucleus vestibularis lateralis - Vem nucleus vestibularis medialis - Vlt nucleus ventrolateralis thalami - VT nucleus ventrolateralis tegmenti - Zp-flm zona perifasciculus longitudinalis medialis - Zp-NIII zona perinervus oculomotorius     

大鼠外侧巨细胞旁网状核的传出纤维联系——HRP法研究

用HRP轴■顺、逆行追踪法观察了大鼠外侧巨细胞旁网状核(PGCL)的传出纤维联系。结果表明:①PGCL经轴■顺行传递,可投射到与痛觉及其调控有关的核团,如脊髓背角、三叉神经脊束核、导水管周围灰质、束旁核、外侧颈核、脑干网状结构核群等;PGCL还投射到与调节内脏活动有关的孤束核、迷走神经背核、导水管周围灰质背份、臂旁核、脊髓侧角等;也向三叉神经运动核、下丘等处发出投射纤维。②腰髓注射HRP后,在PGCL中见有较多的标记细胞,主要分布在锥体束外侧和面神经核腹内侧区域,部分细胞亦见于锥体束内及PGCL靠近软脑膜处。③向下丘和孤束核注入HRP以作往返印证,在PGCL见到标记细胞和纤维。     

Dynamic distribution of ERK,p38 and JNK during the development of pancreatic ductal adenocarcinoma

We recently discovered that oncogenic c-kit is highly expressed concomitantly with the development of pancreatic ductal adenocarcinoma (PDAC). Since oncogenic c-kit may activate major pathways of protein tyrosine phosphorylation, we decided to investigate this issue in the major protein phosphorylation cascades. In normal pancreas labeling with antiphosphorylated ERK1/2 (pERK1/2) antibody was mainly confined to islets of Langerhans in close overlapping with insulin containing cells. Phosphorylated p38 (pp38) showed a similar pattern of distribution, while only weak labeling was evident for pJNK and no labeling of pMEK was observed. As expected, general ERK1/2 (gERK1/2), general p38 (gp38), general JNK (gJNK) as well as general MEK (gMEK) were all evident in islets of Langerhans and in the exocrine tissue. In early development of PDAC, pERK1/2 and pp38 retained their localization in islets of Langerhans. Intensive staining of pERK1/2 was also evident in the cancerous ducts, while the labeling with antibodies to pp38 was more moderate. While pJNK staining in islets of Langerhans was weak, with no labeling in the cancerous ducts, antibodies to gJNK revealed intensive staining suggesting the weak staining of pJNK is not due to the lack of the enzyme. In a more advanced stage of PDAC the carcinomas were clearly stained with pERK1/2 and pp38, while moderate staining with pJNK was also evident. In liver metastases, the cancer cells were heavily labeled with all three phospho-MAPKs. It should be noted that the localization of all three kinases was mainly in the cell nuclei. In the more advanced stage of PDAC, heavy labeling was evident using antibodies to gERK1/2, gp38, gJNK and gMEK. However, no labeling to pMEK was evident in parallel sections. Our data suggest that both in normal and cancerous pancreas, most of the MAPK activities are located in islets of Langerhans and cancerous ducts. It is suggested that using inhibitors to protein kinases may attenuate the progression of the disease.     

Histological studies of neuroprotective effects of Curcuma longa Linn. on neuronal loss induced by dexamethasone treatment in the rat hippocampus

Long term exposure to dexamethasone (Dx) is associated with brain damage especially in the hippocampus via the oxidative stress pathway. Previously, an ethanolic extract from Curcuma longa Linn. (CL) containing the curcumin constituent has been reported to produce antioxidant effects. However, its neuroprotective property on brain histology has remained unexplored. This study has examined the effects of a CL extract on the densities of cresyl violet positive neurons and glial fibrillary acidic protein immunoreactive (GFAP-ir) astrocytes in the hippocampus of Dx treated male rats. It showed that 21days of Dx treatment (0.5 mg/kg, i.p. once daily) significantly reduced the densities of cresyl violet positive neurons in the sub-areas CA1, CA3 and the dentate gyrus, but not in the CA2 area. However, CL pretreatment (100 mg/kg, p.o.) was found to significantly restore neuronal densities in the CA1 and dentate gyrus. In addition, Dx treatment also significantly decreased the densities of the GFAP-ir astrocytes in the sub-areas CA1, CA3 and the dentate gyrus. However, CL pretreatment (100 mg/kg, p.o.) failed to protect the loss of astrocytes in these sub-areas. These findings confirm the neuroprotective effects of the CL extract and indicate that the cause of astrocyte loss might be partially reduced by a non-oxidative mechanism. Moreover, the detection of neuronal and glial densities was suitable method to study brain damage and the effects of treatment.