Development of adaptive behaviour of the respiratory network: implications for the pontine Kölliker-Fuse nucleus

Breathing is constantly modulated by afferent sensory inputs in order to adapt to changes in behaviour and environment. The pontine respiratory group, in particular the Kölliker-Fuse nucleus, might be a key structure for adaptive behaviours of the respiratory network. Here, we review the anatomical connectivity of the Kölliker-Fuse nucleus with primary sensory structures and with the medullary respiratory centres and focus on the importance of pontine and medullary postinspiratory neurones in the mediation of respiratory reflexes. Furthermore, we will summarise recent findings from our group regarding ontogenetic changes of respiratory reflexes (e.g., the diving response) and provide evidence that immaturity of the Kölliker-Fuse nucleus might account in neonates for a lack of plasticity in sensory evoked modulations of respiratory activity. We propose that a subpopulation of neurones within the Kölliker-Fuse nucleus represent command neurones for sensory processing which are capable of initiating adaptive behaviour in the respiratory network. Recent data from our laboratory suggest that these command neurones undergo substantial postnatal maturation.     

Development of adaptive behaviour of the respiratory network: implications for the pontine Kolliker-Fuse nucleus

Breathing is constantly modulated by afferent sensory inputs in order to adapt to changes in behaviour and environment. The pontine respiratory group, in particular the Kolliker-Fuse nucleus, might be a key structure for adaptive behaviours of the respiratory network. Here, we review the anatomical connectivity of the Kolliker-Fuse nucleus with primary sensory structures and with the medullary respiratory centres and focus on the importance of pontine and medullary postinspiratory neurones in the mediation of respiratory reflexes. Furthermore, we will summarise recent findings from our group regarding ontogenetic changes of respiratory reflexes (e.g., the diving response) and provide evidence that immaturity of the Kolliker-Fuse nucleus might account in neonates for a lack of plasticity in sensory evoked modulations of respiratory activity. We propose that a subpopulation of neurones within the Kolliker-Fuse nucleus represent command neurones for sensory processing which are capable of initiating adaptive behaviour in the respiratory network. Recent data from our laboratory suggest that these command neurones undergo substantial postnatal maturation.     

Identification of pathways involved in the natriuretic, kaliuretic and diuretic responses induced by cholinergic stimulation of the medial septal area (MSA)

Natriuresis, kaliuresis and diuresis have been studied in rats following water loading and cholinergic stimulation in the MSA before and after bilateral electrolitic lesion of the habenula, or medullary stria, or supraoptic nucleus or paraventricular nucleus, or fornix. Carbachol injection in MSA elicited an increase of natriuresis and kaliuresis. These responses were blocked by bilateral electrolytic lesion of the habenula, medullary stria, or supraoptic nucleus but not of the paraventricular nucleus or the fornix. Urinary output plotted as a function of time showed antidiuresis in periods of 20 and 40 minutes after carbachol injection into the MSA. The lesion of the supraoptic nucleus inhibited this antidiuresis and natriuresis. The lesion of the habenula or medullary stria blocked natriuresis but not antidiuresis suggesting an independence between the mechanisms of antidiuretic hormone release and natriuresis regulation. The integrity of the habenula, medullary stria and supraoptic nucleus seems to be important in the mediation of the natriuretic response induced by carbachol injection into the MSA.     

The morphology of neurons in trigeminal nucleus oralis projecting to the medullary dorsal horn (trigeminal nucleus caudalis): a retrograde horseradish peroxidase and Golgi study

This study demonstrates that trigeminal nucleus oralis, the most rostral subdivision of the spinal trigeminal nucleus, contains four morphologically distinct types of small neurons which project to the medullary dorsal horn (trigeminal nucleus caudalis) via descending intratrigeminal pathways. Using the retrograde transport of horseradish peroxidase following injections in the medullary dorsal horn, labeled small neurons with cell bodies ranging from 8-15 microns in diameter are found principally in the ventrolateral portion of the trigeminal nucleus oralis. Most neurons are labeled ipsilaterally throughout the entire rostrocaudal extent of the ventrolateral portion of the trigeminal nucleus oralis, but a few cells are also labeled contralaterally. From this aspect of the present study it can be concluded that a specific portion of the trigeminal nucleus oralis, i.e. the ventrolateral part, contains numerous small neurons which send descending projections to the medullary dorsal horn that could affect synaptic activity there. Utilizing both the methods of Golgi and retrograde horseradish peroxidase labeling four distinct types of small descending medullary dorsal horn projection neurons can be distinguished in the ventrolateral portion of the trigeminal nucleus oralis on the basis of their morphology and the distribution of their axons and dendrites. All four neuronal cell types are present throughout the entire rostrocaudal extent of the trigeminal nucleus oralis. Type I neurons are the most frequently labeled descending medullary dorsal horn projection neurons. They are concentrated in the medial 500-550 microns of the ventrolateral portion of the trigeminal nucleus oralis and display dendritic trees which occupy spherical domains approaching 300 microns in diameter. The unmyelinated axons of many of these cells arise either directly from the cell body or a primary dendrite and give rise to a single collateral within 50 microns of their site of origin. This collateral generates a fine axonal plexus within a portion of the dendritic arbor of the parent cell while the parent axon, without branching further, travels a short distance in the ventrolateral portion of the trigeminal nucleus oralis and enters a deep axon bundle. Type II neurons are the second most frequently labeled descending medullary dorsal horn projection neuron. They generate medial and lateral dendritic arbors which together span nearly the entire medial 500-550 microns of the ventrolateral portion of the trigeminal nucleus oralis. An unmyelinated axon emerges from the cell body and within 10-30 microns of its origin gives rise to two collaterals.(ABSTRACT TRUNCATED AT 400 WORDS)     

The projection of low-threshold muscle afferents of the forelimb to the main and external cuneate nuclei of the monkey

The bulbar relay subserved by primary muscle afferents from the monkey's deep radial nerve was investigated by means of transganglionic labeling with wheatgerm agglutinin conjugated with horseradish peroxidase as well as by electrophysiological techniques. It was found that the "deep" input was confined to the pars triangularis of the main cuneate nucleus and to the ventromedial segment of the external cuneate nucleus. On the other hand, labeling occurring following incubation of the superficial (cutaneous) branch of the radial nerve was limited to the pars rotunda of the main cuneate nucleus. The cytoarchitectonic differentiation of the medullary relays is thus met by a clear-cut submodality segregation.     

The interrelations between cell groups in the caudal diencephalon of the rat projecting to the striatum and to the medulla oblongata

Summary In order to investigate the topographical relationships between the caudal diencephalic cells of origin of ascending and descending projections in the rat, one fluorescent retrograde tracer was injected into the striatum and another into the medulla oblongata. The medullary injections were mainly centered in the inferior olive. Cells labeled from the striatal injections densely filled the thalamic parafascicular nucleus. Cells labeled from the medullary injections were seen ventrally to the fasciculus retroflexus in the subparafascicular nucleus. The two populations were mixed in a small area at the ventromedial border of the fasciculus retroflexus. No double labeled cells were observed. The present results indicate that caudal diencephalic cells which ascend to the striatum are different from those descending to the medulla oblongata and that they partially overlap.Supported in parts by CNR grants N. 80.00515-04, 81.00283.04     

Medullary control of the pontine swallowing neurones in sheep

Summary The origin of the inputs from the medullary swallowing centre (dorsal region including the nucleus of the solitary tract, or ventral region corresponding to the reticular formation surrounding the nucleus ambigous) to the pontine swallowing neurones (PSNs) was studied in sheep anaesthetized with halothane.Out of 101 PSNs located in the posterior part of the trigeminal (Vth) motor nucleus, 46 were activated by stimulating either the dorsal (21 neurones) or the ventral (25 neurones) region of the ipsilateral medullary swallowing centre, 3–4 mm rostral from the obex. Thirty-one neurones out of the 46 were identified as a motoneurones supplying swallowing muscles (mylohyoïd, anterior body of digastric and medial pterygoïd). Their average activation latency through stimulation of the dorsal medullary region was about 1 ms longer than through stimulation of the ventral region (3.63 ms±0.81 versus 2.72 ms±0.32).To determine the origin of the medullary input to the PSNs, we tried to activate the medullary swallowing neurones (MSNs) antidromically through stimulating the posterior part of the Vth motor nucleus, which contains the swallowing motoneurones. Seventy-three MSNs were tested (25 located in the dorsal and 48 in the ventral region). None of the dorsal neurones tested could be antidromically activated by pontine stimulation: 15 ventral neurones showed a clear antidromic response (collision test) with an average latency of 2.5 ms±0.73. These neurones, which send their axons into the pons, were all located in the reticular formation, above the nucleus ambiguus, 3–4 mm rostral from the obex.These results suggest that MSNs in the ventral reticular formation connect the medullary swallowing centre to the Vth motor nucleus. They also suggest that during swallowing, inputs originating from the dorsal region of the medullary centre (interneurones programming the motor sequence) are relayed in the ventral region (reticular formation adjacent to the nucleus ambiguus) before reaching the PSNs.This work was supported, in part, by grants from CNRS (LA 205), INRA and M.R.I. (82 E 0685)     

The mormyrid brainstem--II. The medullary electromotor relay nucleus: an ultrastructural horseradish peroxidase study

The medullary relay nucleus of the mormyrid weakly electric fish Gnathonemus petersii is a stage in the command pathway for the electric organ discharge. It receives input from the presumed command or pacemaker nucleus and projects to the electromotoneurons in the spinal cord. Its fine structure and synaptology were investigated by electron microscopy. The origin of the terminals contacting the cell membrane of the neurons of this nucleus was determined by horseradish peroxidase (HRP) injections into different brain structures, namely into the bulbar command- and mesencephalic command-associated nuclei. Twenty-five to thirty large cells of about 45 micron in diameter constitute the medullary electromotor relay. Each cell has a kidney-shaped, lobulated nucleus, a large myelinated axon with a short initial segment and several long, richly arborizing primary dendrites. Many, if not all, cells are interconnected with large somatosomatic or dendrosomatic, dendrodendritic and dendroaxonic gap junctions. These junctions often occur in serial or triadic arrangements. The relay cells receive large club endings as well as small boutons. The club endings are found mainly on the soma and primary dendrites and are morphologically mixed synapses. The boutons are characterized by synapses which are only chemical and are distributed all over the cell membrane, but with a definitely higher frequency on secondary dendrites and more distal parts of dendritic processes. Horseradish peroxidase injections into the mesencephalic command-associated nucleus reveal a large number of labelled boutons on the secondary dendrites of the relay cells. Injections into the bulbar command-associated nucleus label the same type of boutons as mesencephalic injections, but also label club endings on relay cell soma and primary dendrites. The results support the conclusion made on the basis of previous light microscopical observations that boutons originate from the bulbar command-associated nucleus, whereas the club endings issue from the presumed pacemaker nucleus (nucleus c). The club endings of the bifurcating axons of this nucleus are labelled by retro- and anterograde transport of horseradish peroxidase; the bifurcating axons project simultaneously to the bulbar command-associated nucleus and the medullary relay nucleus.     

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8‐month‐old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio‐respiratory control.     

Distribution of premotor neurons for orbicularis oculi motoneurons in the cat, with particular reference to possible pathways for blink reflex

After injecting horseradish peroxidase into the facial nucleus regions containing orbicularis oculi motoneurons, labeled neuronal cell bodies were found in the lateral medullary reticular formation, pretectal olivary nucleus, sensory trigeminal nuclei, lateral and medial parabrachial nuclei, ventromedial reticular formation medial to the facial nucleus, red nucleus and its surroundings, anterior horn of the upper cervical cord, medullary raphe nuclei, oculomotor nucleus and its surroundings, nuclei of Darkschewitsch, Cajal and Edinger-Westphal, ventral part of the midbrain central gray, pontine tegmentum, lateral vestibular nucleus and deep layers of the superior colliculus.     

Projection of the cerebellar dentate nucleus onto the frontal association cortex in monkeys

Summary Stimulation of the cerebellar dentate nucleus in monkeys elicited responses in the frontal association cortex (area 9) on the contralateral side to the stimulation, in addition to those in the motor (area 4) and premotor (area 6) cortices which were reported previously.The responses in the frontal association cortex were characterized by surface positive-deep negative field potentials in the cortex. They contrasted with surface negative-deep positive potentials in the motor and premotor cortices on the same dentate nucleus stimulation. In the rostral part of the premotor cortex (area 6) on the border of area 9, both types of responses were induced and admixed.The relay nucleus of the thalamus was suggested for the dentate-induced responses in the frontal association cortex.     

Pyramidal input to the intracerebellar nuclei of the cat

In unanesthetized cats it has been found that pyramidal volleys elicited upon medullary pyramidal tract stimulation were capable of modifying the discharge of 41% of intracerebellar nuclear cells, via pontocerebellar systems impinging predominantly on the lateral cerebellar cortex. The incidence of responsive cells was 80% in the dentate nucleus compared with 10% in the fastigial nucleus, 11% in the anterior and 12% in the posterior division of the interpositus nucleus. The response was in 59% of the cases excitation followed by inhibition, in 30% of the cases a pure excitation and in 11% of the cases a pure inhibition. Excitation, pure or followed by inhibition, had a mean latency of 5.78 ms and a mean duration of 12.21 ms, while inhibition displayed a mean latency of 9.03 ms and a mean duration of 34.64 ms. The possible functional significance of the pyramidal input to the lateral cerebellum is briefly discussed in relation to a possible convergence of pyramidal and associative impulses in single cerebellar neurons.     

The mormyrid brainstem--III. Ultrastructure and synaptic organization of the medullary "pacemaker" nucleus

The ultrastructure and synaptic organization of the presumed medullary pacemaker nucleus, nucleus c of the weakly electric mormyrid fish, Gnathonemus petersii has been investigated. Nucleus c consists of about 12-15 small (20-25 micron) neurones (P-cells), which form a group situated ventrally to the medullary relay nucleus and embedded in a neuropil of myelinated fibres and dendritic processes. The P-cells often exhibit an enhanced electron density of their cytoplasm and dendroplasm. They possess several dendrites of different diameter, a short, thin axon initial segment and a thickly myelinated axon running in dorsal direction. The pacemaker neurons are interconnected by complex electronic coupling, established by somatosomatic, dendrosomatic and dendrodendritic gap junctions. Perikarya and dendrites are frequently interconnected serially by gap junctions; dendrites showed sometimes triadic gap-junction arrangement. It is suggested that this high degree of electrotonic coupling amongst the pacemaker cells represents the first level of the highly ordered synchronization processes which characterize the electric discharge command system of Gnathonemus. Pacemaker cells receive synaptic input from club endings with mixed synapses and from bouton-like terminals with chemical synapses, both of them originating from medium-sized myelinated fibres and contacting mainly neuronal perikarya and dendritic processes. The axon initial segment receives only few synaptic inputs. Bouton-like terminals were found to be of two types according to their vesicle content, namely, boutons with ovoid, clear synaptic vesicles forming Gray type-1 synapses and boutons with pleomorphic clear synaptic vesicles forming Gray type-2 synapses. Different functional roles for the two types of boutons in modulating pacemaker cell activity are suggested.     

Microvascular patterns in human medullary tegmentum at the level of the area postrema

Abstract The aim of the present study was to evaluate the regional differences in microvessel density (MVD) of the human medullary tegmentum in adults and newborns/infants. Transverse serial sections of formalin-fixed, paraffin-embedded brainstems, taken from 16 adult and eight newborn/infant subjects, were stained with anti-von Willebrand factor (vWF) polyclonal antibodies. The boundaries of the area postrema (AP), dorsal motor vagal nucleus (DMVN), solitary tract nucleus (STN), solitary tract (ST) and hypoglossal nucleus (XII) were defined, all vessels were counted and the values were divided by the areas. In adult cases, statistically significant heterogeneity in MVD was found among the nuclei studied (P < 0.001). DMVN and AP showed higher MVD with respect to XII and ST (P < 0.001). The MVD of STN was lower with respect to DMVN (P < 0.001) and higher with respect to XII and ST (P < 0.05). The MVD and capillary density of the AP of newborns/infants were not significantly different with respect to adults. In sections of the medulla of adult subjects stained with anti-vWF, all vessels showed an intense reaction of endothelial cells whereas in the DMVN, XII, STN and ST of newborns/infants, only rare, isolated vessels showed anti-vWF reactivity and in the AP, 41 +/- 21% of vessels expressed vWF. Differences in MVD among the nuclei may be related to their different functions and metabolic demands. Light and heterogeneous expression of vWF in endothelial cells of newborns/infants indicates that differentiation of microvasculature in the human medullary tegmentum extends beyond fetal stages.     

Energetics and oxygen transport mechanisms in embryos

Abrupt, bilateral destruction of the pre-Bötzinger Complex (preBötC) leads to terminal apnea in unanesthetized goats and rats. In contrast, respiratory rhythm and pattern and arterial blood gases in goats during wakefulness and sleep are normal after incremental (over a month) destruction of >90% of the preBötC. Here, we tested the hypothesis that the difference in effects between abrupt and incremental destruction of the preBötC are a result of time-dependent plasticity, which manifests as anatomic changes at sites within the respiratory network. Accordingly, we report data from histological analyses comparing the brainstems of control goats, and goats that had undergone bilateral, incremental, ibotenic acid (IA)-induced preBötC lesioning. A major focus was on the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pontine respiratory group (PRG), which are sites thought to contribute to respiratory rhythmogenesis. We also studied the facial (FN), rostral nucleus ambiguus (NA), medullary raphé (MRN), hypoglossal (HN), and the dorsal motor vagal (DMV) nuclei. Neuronal counts, count region area (mm²), and neuronal densities were calculated using computer-assisted analyses and/or manual microscopy to compare control and preBötC-lesioned animals. We found that within the ventral and lateral medulla 2 mm rostral to the caudal pole of the FN (presumed pFRG/RTN), there were 25% and 65% more (P < 0.001) neurons, respectively, in preBötC-lesioned compared to control goats. Lesioned goats also showed 14% and 13% more (P < 0.001) neurons in the HN and medial parabrachialis nucleus, but 46%, 28%, 7%, and 17% fewer (P < 0.001) neurons in the FN, NA, DMV, and Kölliker-Fuse nuclei, respectively. In the remaining sites analyzed, there were no differences between groups. We conclude that anatomic changes at multiple sites within the respiratory network may contribute to the time-dependent plasticity in breathing following incremental and near-complete destruction of the preBötC.     

Autoradiographic localization of substance P receptors in rat medulla: effect of vagotomy and nodose ganglionectomy

Light microscopic autoradiography of [125I]Bolton-Hunter substance P binding sites was used to study the localization and denervation-induced changes in substance P receptors in the medulla oblongata. Substance P binding sites were widely distributed. The highest density was in the rostral nucleus ambiguus, dorsal motor nucleus of the vagus, nucleus of the solitary tract, hypoglossal nucleus, spinal trigeminal nucleus and inferior olive. Moderate density was apparent in the commissural nucleus of the solitary tract, area postrema, parvocellular reticular nucleus, medial vestibular nucleus and facial nucleus. The remainder of the medullary nuclei contained few or no specific substance P binding sites. Specific binding was inhibited by the addition of unlabeled substance P (1 microM). The association of substance P binding sites with the spinal trigeminal nucleus and with several nuclei involved in autonomic function suggest a role for substance P receptor activation in nociceptive and autonomic regulation, respectively. To study the influence of afferent and efferent denervation, the substance P binding sites in the medulla of sham operated rats were compared with those of both unilateral nodose ganglionectomized and cervical vagotomized rats. Substance P binding was unilaterally reduced in the rostral nucleus ambiguus and the rostral dorsal motor nucleus of the vagus with either surgical procedure. No changes in substance P binding were detected in other medullary nuclei, including the nucleus of the solitary tract, the site of termination of afferent vagal fibers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative Characteristics of Respiratory Pattern Responses to Microinjection of Kainic Acid into Different Parts of the Nucleus Ambiguus

Experiments on anesthetized rats were performed using local chemical exclusion of neurons with kainic acid to study the relative roles of the rostral, intermediate, and caudal parts of the nucleus ambiguus in the mechanisms controlling respiration. The characteristics of the respiratory rhythm and pattern responses to chemical exclusion of different parts of this nucleus were observed. In particular, sequential exclusion of the left and right rostral parts of the nucleus ambiguus reproducibly induced significant decreases in the respiration rate and respiratory volume in the first minutes; in 83% of experiments, there was also irreversible respiratory arrest. Exclusion of symmetrical intermediate parts of the nucleus ambiguus was followed by bradypnea and decreases in pulmonary ventilation, the greatest respiratory effects being noted only after injection of kainic acid into the second symmetrical area, irreversible respiratory arrest being seen in 50% of cases. Exclusion of symmetrical caudal areas of the nucleus ambiguus resulted only in small decreases in respiratory frequency without significant changes in respiratory volume and gave rise to the smallest incidence of respiratory arrest, i.e., 33%.     

Topographic principles in the spinal projections of serotonergic and non-serotonergic brainstem neurons in the rat

The spinal projections from the raphe-associated brainstem areas containing serotonergic neurons were studied with aldehyde-induced fluorescence in combination with the retrograde fluorescent tracer True Blue in the rat. This technique makes it possible to determine simultaneously the projections of individual neurons and to detect whether serotonin is present in the same neurons. After tracer injections into the spinal cord retrogradely labeled serotonergic and non-serotonergic neurons were found in the medullary raphe nuclei and adjacent regions and to a lesser extent in association with the dorsal and median raphe nuclei in the mesencephalon. Large True Blue injections that covered one side of the spinal cord at mid-cervical level labeled about 60% of the ipsilaterally situated serotonergic neurons in the medullary raphe regions while the corresponding figure contralaterally was about 25%. On both sides a larger number of labeled non-serotonergic neurons were found; these were sometimes located dorsal to, but often intermingled with, the serotonergic cells. While the serotonergic projection from the mesencephalon could not be labeled from injections below cervical levels, the labeling in more caudal brainstem regions exhibited only minor variations depending on the rostrocaudal level of the spinal segment injected. Furthermore, quantitative data from injections at different levels indicate that the majority of the spinal-projecting neurons traverse most of the length of the cord. Summarizing the results obtained from small injections restricted to subregions of the cord we feel that it is possible to distinguish three fairly distinct pathways for spinal projections from the medullary raphe and adjacent regions: The dorsal pathway originates mainly from cells in the caudal pons and rostral medulla oblongata (rostral part of nucleus raphe magnus, nucleus raphe magnus proper, nucleus reticularis gigantocellularis pars alpha and nucleus paragigantocellularis). This pathway, which contains a large non-serotonergic component, descends through the dorsal part of the lateral funiculus and terminates mainly in the dorsal horn at all spinal cord levels. The intermediate pathway is largely serotonergic with its cell bodies located within the arcuate cell group (situated just ventral and lateral to the pyramids very close to the ventral surface of the brainstem) and in the nucleus raphe obscurus and pallidus and terminates in the intermediate grey at thoracolumbar and upper sacral levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Development of topographic connections between the isthmic nuclei and optic tecta in the frog Limnodynastes dorsalis

Summary In the frog Limnodynastes dorsalis, the pattern of topographic connections between the isthmic nuclei and optic tecta was determined by anterograde and retrograde transport of horseradish peroxidase from localised tectal regions. In both larvae and adults, reciprocal mapping of the uncrossed isthmo-tectal and tecto-isthmal projections was evidenced by the juxtaposition of labelled tecto-isthmal terminations with labelled cells in the cortex and medulla of the ipsilateral isthmic nucleus. The crossed isthmo-tectal projection was revealed by labelled cells in the cortex and medulla of the nucleus contralateral to the injection.In adults, rostral tectal areas projected to rostral and ventral regions of the ipsilateral isthmic nucleus. Following more caudal tectal injections, labelled cells were found in progressively more dorsal locations within the nucleus. Labelled cells in the contralateral nucleus were found in the rim cortex abutting a neuropil and in medullary cells adjacent to this region. Connections between ventral isthmic regions and most rostral tectum and between dorsomedial nucleus and caudomedial tectum were similar in both nuclei. However, for isthmic areas projecting to rostromedial and mid-tectum, the location of labelled cells in the contralateral nucleus was inverted with respect to the ipsilateral nucleus. This inversion would allow both nuclei to project to visually corresponding regions of each tectum.During larval stages the basic adult topography was established despite the continued neurogenesis of both isthmic nuclei and optic tecta. In late larval stages a rim neuropil appeared adjacent to the cortical region in the isthmic nuclei where labelled cells of the crossed isthmotectal projection were found. Prior to this stage labelled cells abutted labelled medullary cells. The appearance of this neuropil was approximately temporally correlated with the onset of electrophysiologically detectable responses in the ipsilateral visuotectal projection. Formation of the rim neuropil may relate to maturation of the tecto-isthmo-tectal connections which underlie this visual projection.     

大鼠臂旁核内nNOS阳性传入纤维的脑内来源

目的探讨大鼠臂旁核(PBN)内神经元型一氧化氮合酶(nNOS)阳性传入纤维的脑内来源。方法在大鼠PBN内微量注射荧光金(FG),结合nNOS免疫荧光双标技术,观察FG/nNOS双标神经元在脑内的分布情况。结果FG/nNOS双标神经元主要分布在孤束核(NST)、延髓嘴侧腹外侧区(RVL)、中缝背核(DR)、导水管周围灰质(PAG)和下丘脑室旁核(PVN)。结论NST、RVL、DR、PAG和PVN内的nNOS阳性投射神经元是PBN内nNOS阳性纤维终末的主要来源。