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N J Lenn

Publications and source records attributed to N J Lenn.

13 recordsLinked to original sources

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

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

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

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

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

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

A simple apparatus for controlled pressure perfusion fixation.

An apparatus is described for vascular perfusion of small animals with fixative solutions which while simple and inexpensive allows quantitative and reproducible pressure control. Direct measurement of outflow pressure demonstrated that a sphygmomanometer used to supply external pressure to a plastic blood transfer pack achieved these features. Reproducibility of pressure was maintained by filling the bag with air between perfusions, or when smaller volumes of fixative solution were needed. Rodent brains from fetal to adult ages, and other animals of similar size, have been reliably well fixed by this method.

Animals

Synapses in the interpeduncular nucleus: electron microscopy of normal and habenula lesioned rats.

Four types of synapses have been identified in the rat interpeduncular nucleus. The S synapses were formed by the mainhorizontal plexus of habenulointerpeduncular axons. They contained spherical synaptic vesicles and formed asymmetrical en passant contacts with dendritic processes. The crest synapses had all of these features in common with the S synapses, but occurred in pairs with the two contact zones coextensive and largely parallel on opposite sides of markedly attenuated dendritic processes. Synaptic glomeruli found in this nucleus consisted of several crest synapses engulfed by sheet-like dendritic processes. Identical crest synapses also occurred on dendritic crests. In a limited number of cases, both S and crest synapses arose in common from single axons. Following destruction of the habenular nuclei unilaterally or bilaterally, as expected from the above observations, both S and crest synapses underwent dense degeneration. In some cases with bilateral lesions and in all cases with unilateral lesions, only one of the two axonal endings forming a crest synapse degenerated while the other remained unaffected. Axons containing flat vesicles forming symmetrical axodendritic synapses, axosomatic synapses, and subjunctional bodies associated with S or crest synapses were all minor features of this nucleus. Aspects of the unusual synaptology of this nucleus are discussed in terms of morphology, physiology and transmitter chemistry.

Animals

Neurological assessment of patients on prolonged methadone maintenance.

Medical histories, neurological examinations and electroencephalograms of 25 methadone-maintained subjects were compared with those of 25 abstinent controls. Comparisons on all measures failed to show significant differences between groups. The incidence of abnormalities was low for all subjects. None of the observed conditions appeared to involve methadone in their etiology.

Adult

Fornix afferents to the anteroventral thalamic nucleus: an EM study in the rat.

Three types of synapses occur in the anteroventral thalamic nucleus (AVN). Type 1 consists of small (0.5-0.8 microns) axonal endings densely packed with spherical synaptic vesicles. They form markedly asymmetrical synaptic contacts with distal portions of dendrites. Degenerative changes in these axons following destruction of the fornix identify them as the endings of the subicular projection to AVN. Type 2 synapses consist of large (1.0-1.5 microns) axonal processes containing spherical vesicles which form asymmetrical synapses on more proximal dendrites. Type 3 endings consist of large unidentified processes containing spherical, and occasionally flattened, synaptic vesicles forming symmetrical contacts with the largest stem dendrites. Neither of these synaptic types were modified by fornix lesions. The synaptic arrangements within AVN are simpler than other thalamic nuclei in that serial synapses and synaptic glomeruli are not present.

Afferent Pathways

Quantitative demonstration of somatic synapse sprouting following dendritic deafferentation in neonatal rat interpeduncular nucleus.

Neonatal habenular lesions deafferent the dendrites of interpeduncular nucleus (IPN) neurons by preventing formation of S and crest synapses. The small number of synapses normally contacting IPN neuronal perikarya are of unknown, but non-habenular, origin. The number of synapses on IPN perikarya is significantly increased (p less than 0.001) when 10 control animals are compared to 7 animals with unilateral habenular lesions and 7 animals with bilateral lesions. The increases with bilateral lesions are approximately twice those resulting from unilateral lesions (p less than 0.01). This phenomenon involves sprouting of both the somatic synapses which contain spherical vesicles and those with flattened vesicle endings, and is greater when the latter are considered alone (p less than 0.001). Only the small group of somatic synapses with asymmetrical contacts failed to show a change. The increases suggest a postsynaptic control mechanism which acts in the direction of preserving synaptic input, but permits displacement of the site of input from dendrites to soma. Factors which may be important in determining this outcome are the production of the lesions prior to synaptogenesis, and the presumed shrinkage of the dendrites of the IPN neurons.

Animals