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Biomedical subjects

N J Lenn

Publications and source records attributed to N J Lenn.

At least 37 records · Page 2Linked to original sources
PubMed1985

Choline acetyltransferase immunoreactivity is localized to four types of synapses in the rat interpeduncular nucleus.

The cholinergic synapses of the rat interpeduncular nucleus (IPN) were demonstrated by immunostaining that utilized a monoclonal antibody directed against choline acetyltransferase. The rostral, central, intermediate and lateral subnuclei of the IPN each contained a single type of immunoreactive terminal. Immunoreactivity was localized to synaptic vesicle membranes (especially at the contact zones), and longitudinal microtubules in preterminal portions of axons. Terminals were identified by comparison to previous studies of the synaptic organization of the IPN. In the rostral subnucleus, the immunoreactive terminals were characterized by their content of spherical vesicles, 45 nm in diameter, intermixed with moderate numbers of dense-cored vesicles, 75-100 nm in diameter. These terminals formed asymmetrical contacts. They correspond to the more numerous of the two types of axodendritic terminals described in this subnucleus, i.e. those which degenerate after lesions of the habenula. The moderate number of immunoreactive terminals in the lateral subnucleus contained pleomorphic vesicles, 30-45 nm in diameter. Up to three of these formed symmetrical contacts with individual dendrites, which ranged in diameter from 0.35 to 0.55 micron. The other types of axodendritic terminal in this subnucleus, which often contacted the same dendrites, were unstained. These latter terminals have been interpreted as being those which contain substance P. The immunoreactive terminals in the diameter, and formed markedly asymmetrical en passant contacts with small dendritic processes or spines. The immunoreactive terminals in the intermediate subnucleus had the same presynaptic and contact morphology. Many were clearly crest synapses. The remainder appeared to be such, but seen only partially within the plane of section. In the intermediate subnucleus there were up to several hundred immunostained terminals per grid square in some sections. These findings are consistent with the existence of a dense cholinergic projection to the IPN. The habenular region, are shown to crest and S synapses, both of which generate after lesions of the cholinergic innervation of other subnuclei of the IPN increases understanding of the relation of cholinergic to other transmitters localized to various portions of this nucleus.

Animals↗
PubMed1985

Gestational changes in the germinal matrix of the normal rhesus monkey fetus.

To explain the reported predisposition to germinal matrix hemorrhage in premature infants, pathogenetically important morphological features of the germinal matrix should be present in the 3rd trimester and rapidly change near term. Such features were sought in this study of the germinal matrix and its vasculature in normal rhesus monkey fetuses. The matrix cells, glia, ependyma, and capillaries showed no important structural changes during the 3rd trimester. The terminal vein tributaries were greatly enlarged by 148 days, but cellular and collagen support in their walls was minimal at this time. The latter features developed by the final days of gestation. These findings do not support a structural immaturity or specialization of the germinal matrix predisposing to germinal matrix hemorrhage. Our results, therefore, support the recent emphasis on physiological parameters in the pathogenesis and prevention of germinal matrix hemorrhage.

Animals↗
PubMed1984

The subnuclear distribution of substance P, cholecystokinin, vasoactive intestinal peptide, somatostatin, leu-enkephalin, dopamine-beta-hydroxylase, and serotonin in the rat interpeduncular nucleus.

The distribution of immunofluorescent somata and processes within the interpeduncular nucleus (IPN) containing substance P (SP), cholecystokinin (CCK), vasoactive intestinal peptide (VIP), somatostatin (SST), leu-enkephalin (L-ENK), dopamine beta hydroxylase (DBH), and serotonin (5HT) was examined in male rats treated with colchicine 48 hours prior to perfusion. Serial sections were examined for immunofluorescence and variations in the density of fluorescence rated 1 + (sparse) to 4 + (dense). The rostral subnucleus contained SP, SST, and L-ENK-positive somata and processes. Substance P and VIP processes were present throughout the rostral subnucleus but were concentrated in two ovoid areas located dorsally in the caudal region of this subnucleus. Cholecystokinin and L-ENK processes surrounded these ovoid areas. The entire width of the central subnucleus was crossed by SP and L-ENK processes oriented horizontally in narrow bands. Substance P processes were also aligned into vertical columns adjacent to the lateral margins of the central subnucleus. Leu-enkephalin and 5HT processes were distributed throughout this subnucleus, while VIP processes were present only caudally. Dopamine beta hydroxylase processes were evenly distributed but were restricted from the vertical columns laterally. The intermediate subnuclei contained a sparse density of SP and 5HT processes that were present in proximity to the major blood vessels penetrating this subnucleus. Only DBH processes were evenly distributed. The lateral subnuclei contained a dense concentration of SP processes. The medial edges of this subnucleus were distinguished by VIP, CCK, L-ENK, and 5HT processes. The dorsal subnucleus contained 5HT, L-ENK, and SST-positive somata and processes. Substance P, VIP, CCK, and DBH processes were also present. Dorsal-lateral subnuclei contained SP, SST, L-ENK, and DBH processes. Interstitial subnuclei contained SP, CCK, L-ENK, 5HT, and DBH processes. This study demonstrates that perikarya and processes containing peptides and monoamines are distributed within subnuclei of IPN in a topographic and heterogeneous pattern. New features of IPN organization are revealed.

Animals↗
PubMed1984

The subnuclear organization of the rat interpeduncular nucleus: a light and electron microscopic study.

The subnuclear organization of rat interpeduncular nucleus (IPN) has been examined by light microscopy following staining with Nissl and Holmes methods, 3H-leucine autoradiography, acetylcholinesterase (AChE), and cytochrome oxidase histochemistry on plastic sections stained with toluidine blue, and by electron microscopy. Three unpaired and four paired subnuclei are recognized. The rostral subnucleus is heavily stained for AChE, which clearly delineates its borders. It is distinguished ultrastructurally by two types of synapses on dendrites, and two on perikarya. Of the former, one type is formed by presynaptic processes which contain spherical and dense-cored vesicles and make asymmetrical contacts. Dense-cored vesicles are observed in many of the postsynaptic dendrites. A second type has presynaptic processes containing small, pleomorphic vesicles which make symmetrical contacts. Synapses on perikarya are found in the rostral, central, intermediate, lateral, and interstitial subnuclei. The dorsal subnucleus is continuous with the serotonin-containing B8 cells. The central subnucleus is distinguished by longitudinally oriented medial habenular axons separating palisades of cell bodies. These axons, which also traverse the intermediate subnuclei, form en passant S synapses with small dendrites of the central subnucleus. The intermediate subnuclei react faintly for AChE and intensely for cytochrome oxidase. They contain crest synapses formed by two habenular afferents, one from each medial habenula, which contact a narrow dendritic process en passant. The lateral subnuclei react intensely for AChE and have ultrastructural features similar to the rostral subnuclei. The interstitial subnuclei lie within each fasciculus retroflexus as it enters IPN. The small dorsal lateral subnuclei are evident by light microscopy.

Acetylcholinesterase↗
PubMed1984

Subdivisions of the interpeduncular nucleus: a proposed nomenclature.

A compromise terminology for subdivisions is proposed which integrates the two previous standard and two recent and more detailed subnuclear schemes. The unpaired median subnuclei are called rostral, central and apical. The paired subnuclei are called rostral lateral, dorsal lateral, intermediate and lateral. A plea is made for attention to these consistent subdivisions, and for uniformity of terminology regardless of the parameters studied.

Animals↗
PubMed1984

The association of spinal and gastroesophageal anomalies. Case report and review.

Severe cervical radiculopathy occurred in a child with gastroesophageal duplication who had a previously unrecognized vertebral malformation. We review the literature on the association of vertebral and gastroesophageal anomalies and discuss the recent studies in human embryology which detail the relations of notochord to endoderm and neural ectoderm at about 3 weeks of gestation. This case illustrates the opportunity of preventing nerve root or spinal cord compromise due to such vertebral anomalies when the possibility of their association with gastroesophageal duplication is considered.

Abnormalities, Multiple↗
PubMed1983

Left-right pairing at the crest synapses of rat interpeduncular nucleus.

Synaptic terminals of the habenulo-interpeduncular axons in rat interpeduncular nucleus are demonstrated by electron-microscopic autoradiography following [3H]leucine injection into the habenula. The endings are of two types, S and crest synapses. Previous descriptions of the S synapses based on indirect identification were confirmed. The crest synapses in the interpeduncular nucleus consist of two habenular afferents contacting a narrowed dendrite. Injection of both habenulae with radiolabeled amino acid resulted in autoradiographic labeling of both axons at 48% of individual crest synapses, and of one axon at 39%. However, when only one habenula was injected, no more than one axon was labeled at individual crest synapses; this occurred at 59%. Interpretation of unlabeled endings is possible using the "detection rate" of the method (per cent ratio of labeled to total endings). The detection rate, which can be determined for the bilateral injection case, allows recalculation of the raw data for the unilateral injection case. Left-right pairing of habenular afferents actually occurs at approximately 90% of crest synapses. The use of detection rates in this way, additionally exemplified by analysis of an electron-microscopic degeneration study, is also important in many other applications of both of these experimental neuroanatomical methods, especially when comparisons between two sets of data are made. The conclusions of studies which have not taken this problem into account must be interpreted with caution.

Afferent Pathways↗
PubMed1983

Synaptic plasticity within the interpeduncular nucleus after unilateral lesions of the habenula in neonatal rats.

In rats, synaptic terminations of the medial habenular (MH) afferents to the interpeduncular nucleus (IPN) are just beginning to form at the time of birth. The alterations in synaptogenesis resulting from unilateral MH lesions placed in neonatal rats were demonstrated with the autoradiographic and degeneration methods after the operated animals had reached maturity. The distribution of S synapses, en passant MH afferents to the central IPN, is normally 95% ipsilateral to their MH of origin in spite of the fact that their axons cross through the contralateral half of the IPN one or more times. The lesions result in a symmetrical distribution of S synapses from the remaining MH. The density of this projection on each side is equal to the normal ipsilateral density of termination. Crest synapses, present in intermediolateral IPN bilaterally, consist of two endings which contact a narrow dendritic process. Normally, the two endings arise one from each MH at 90% of crest synapses, and two from the same MH at 10%. After unilateral MH lesions in neonates, approximately 96% of crest synapses are formed by two axons from the one remaining MH. At only 4% of crest synapses one or both processes is heterologous, that is, of non-MH origin. These findings demonstrate that synapse formation on IPN neurons preferentially favors MH afferents, both normally and when left-right interaction is precluded by a neonatal unilateral lesion. Left-right interactions normally occur at both the level of the left and right sides of the IPN with regard to S synapses and individual left and right habenular afferents at crest synapses. Plasticity at crest synapses is considerably greater in neonates compared to adult rats. Control of these phenomena can be understood as the interaction of multiple factors. These may include specific determinants localized to the presynaptic axons, particularly prior to synaptogenesis and competition for synaptic space, especially with regard to S synapses and perhaps involving synapse elimination. There is also evidence for postsynaptic determinants both in the separation of synaptic types into separate subnuclei and in the formation of crest synapses in the IPN regardless of the presence of normal or reduced numbers of MH afferents, or their total absence.

Animals↗
PubMed1982

Acute cerebellar ataxia of childhood and optic neuritis with retrochiasmal involvement.

A case of a 4-year-old white girl affected with unilateral optic neuritis and acute cerebellar ataxia is presented. Visual evoked potentials (VEP) demonstrated prolonged latency of the right optic nerve as well as the left retrochiasmal pathways. This child had complete resolution of the cerebellar ataxia and the optic neuritis with return to normal of her VEP. This case is an example of a disease characterized by a single episode of multifocal involvement of the CNS differing from diffuse encephalomyelitis and multiple sclerosis.

Acute Disease↗
PubMed1978

Postnatal synaptogenesis in the rat interpeduncular nucleus.

The rat interpeduncular nucleus (IPN) was studied by electron microscopy from the day of birth to 33 days of age. The habenulointerpeduncular (H-IPN) axons, the principal afferents to IPN, were prominent at birth, occurring in large groups. They formed occasional S synapses en passant at this time. S synapses subsequently increased progressively in number and maturity until 28 days of age. Crest synapses, also formed by the H-IPN axons, appeared at eight days without a recognized formative stage. They exhibited their diverse adult morphology by 14 days of age. F synapses, endings of uncertain origin that contain flattened vesicles, were seen at 21 days, although endings containing small vesicles at 14 days represented the same population. Axosomatic synapses were first seen at four days and remained infrequent subsequently. Dendritic growth cones had their maximal prevalence at birth, decreased at four days and were absent by six days of age. Thus each of the four synaptic types previously described in the adult rat IPN exhibited a characteristic time of appearance and pattern of development in normal rat pups. This well-ordered sequence of synaptogenesis makes the H-IPN system well suited for a study of synaptic plasticity.

Age Factors↗
PubMed1978

Effect of neonatal deafferentation on synaptogenesis in the rat interpeduncular nucleus.

Changes in the normal synaptogenetic pattern of the interpeduncular nucleus (IPN) were induced by destruction of one or both habenular nuclei in neonatal rats. The S synapses, the principal habenulointerpeduncular (H-IPN) afferents, were reduced in number and delayed in time of appearance by unilateral lesions. They were eliminated by bilateral lesions. The crest synapses, also of habenular origin, appeared at ten days of age and were apparently normal in structure after unilateral lesions. However, this actually represented a change in connectivity, since normal crest synapses are of bilateral origin. Following bilateral habenular lesions abnormal crest synapses appeared at 28 days of age. These had normal postsynaptic structure, but presynaptically were formed by non-habenular axons, usually of two different types of each crest synapse. Lesions induced an early appearance of F synapses, at three days, instead of the normal time after six days of age. Apparently similar processes containing flattened vesicles formed somatic contacts only in lesioned animals beginning at 21 days of age. The axosomatic synapses which were only occassional in the adult appeared at the normal time in lesioned animals. At 28 days of age in both unilaterally and bilaterally lesioned animals there was an increase in the number of somatic synapses. This increase was due to an increase of the normal somatic endings plus the appearance of somatic synapses containing flattened vesicles. Both types of somatic contacts were found in similar numbers at subsequent ages up to three months. The changes in S synapses represent Wallerian degeneration. The formation of unilaterally derived crest synapses in unilaterally lesioned animals is interpreted as evidence for a specific recognition mechanism. A postsynaptic control mechanism is proposed to explain the formation of heterologous crest synapses, with the usual distinctive geometry but involving abnormal, non-habenular presynaptic elements four weeks following neonatal bilateral lesions. The increase in axosomatic synapses is unusual since the dendrites of IPN neurons were deafferented, not their somata. The factors leading to the changes in somatic synapses are discussed. The findings reveal new examples of the complexity of neuronal adaptation to CNS lesions in early life.

Afferent Pathways↗
PubMed1978

Development of the interpeduncular nucleus in the midbrain of Rhesus monkey and human.

The development of the interpeduncular nucleus (IPN) in primates was studied in rhesus monkey with 3H-thymidine autoradiographic, Nissl and Golgi methods and in humans in histological preparations from embryos and fetuses of different ages. Autoradiographic analysis demonstrated that the neurons of the monkey IPN underwent their final cell division between postconception day 36 (E36) and E42, which corresponds to Stages 17 through 21 of Hendrickx and Sawyer. Autoradiograms of monkeys sacrificed at various short intervals following exposure to a pulse of 3H-thymidine showed that IPN neurons were generated in the proximity of the ventricular surface near the confluence of the 3rd ventricle and cerebral aqueduct, migrated ventrally along the midline and then spread laterally after reaching the ventral midbrain, where IPN was first recognized at E45 (Stage 23). The distribution of successively generated neurons in autoradiograms revealed caudal to rostal and lateral to medial spatiotemporal gradients. Differentiation of IPN neuronal size and development of Nissl substance began in rhesus monkey only after postmitotic cells had reached their destination and seemed to be pronounced mainly through E104. However, growth of the dendrites and elaboration of their side branches as seen in Golgi impregnations progressed gradually from E81 to birth (E165) and perhaps even later. Analysis of histological preparations of a series of human embryos and fetuses was used to derive similar information indirectly, since the autoradiographic method cannot be applied to man. It was found that IPN neurons in human probably underwent their final division between Carnegie Stage 17 and 21. Similarly, as in monkey, postmitotic cells in human IPN displayed an inverted fountain pattern of cellular migration. IPN could first be delineated at Stage 23. There was evidence for both caudal to rostral and lateral to medial spatiotemporal gradients in the human, as in the monkey. Thus, in monkey and human, all IPN neurons are generated within the first quarter of intrauterine life and there is remarkable similarity in the timing, tempo and pattern of IPN neuronal differentiation in both species, indicating the validity of using nonhuman primates as an experimental model for understanding the development of this structure in man.

Animals↗
PubMed1978

Exacerbation generalized nonconvulsive seizures with ethosuximide therapy.

We describe a patient whose absence seizures increased greatly in number after the addition of ethosuximide to ongoing phenobarbital therapy. This unusual response and review of other cases in the literature suggested the possibility of some as yet underfined interaction between ethosuximide and other anticonvulsant drugs. That a particular subytpe of epilepsy may be worsened by ethosuximide therapy is also considered.

Child↗
PubMed1977

Postnatal development of the suprachiasmatic hypothalamic nucleus of the rat.

Light and electron microscopy of newborn, four day, one, two, three and five week old rats revealed principally a progressive increase in the diversity and number of synaptic contacts in the suprachiasmatic nucleus (SCN). The major increase in synaptic diversity occurred between four days and one week of age. Correlation between this finding and the adult synaptic morphology of SCN (Gülder, 1976) on the one hand, and the ontogeny of circadian rhythms on the other were made. This suggested that the retinal afferents arriving on day four form asymmetrical contacts with dendrites. While increase in synaptic number was progressive, it was most marked between three and five weeks of age. By five weeks, most features of the adult SCN were present. No significant morphological effects were evident as a result of neonatal retinal lesions.

Animals↗
PubMed1977

Fibers in monkey posterior articular nerves.

The distribution of axons in the posterior articular nerves in rhesus monkey has been studied in terms of ratio of myelinated to unmyelinated fibers, and size of myelinated fibers. Conduction velocity measurements were also made. The nerves contained 2,000 to 2,200 unmyelinated fibers of 0.2 to 1.2 mum diameter. They contained 399 to 478 myelinated fibers, varying in size from 1.4 to 12.3 mum. Thus 80 to 85% of fibers in these nerves were unmyelinated. The maximum conduction velocity of 70 to 80 meters per second corresponded to an initial small deflection, with most fibers conducting at slower rates. These results are compared to previous reports which severely underestimated the number of unmyelinated fibers because electron microscope counts were not utilized. It is suggested that pain fibers from the knee joint of monkey make up much of this large population of unmyelinated axons. An unknown number of post-ganglionic sympathetic fibers is also included in the unmyelinated fiber group.

Animals↗