Absence of post-lesion reactive gliosis in elasmobranchs and turtles and its bearing on the evolution of astroglia.

In the mature mammalian and avian central nervous systems, neuronal destructions are followed by reactive gliosis, but data on other vertebrates are rather controversial. Mammals and birds belong to different amniote groups (Synapsida and Diapsida, respectively), but exhibit common general features in their glial architecture, mainly the predominance of astrocytes. Two vertebrate groups seem to be in special positions of glial evolution: turtles (Testudiniformes) and skates and rays (Batoidea). The purely ependymoglial system of turtles seems to be the simplest one among the extant amniotes. In skates and rays, true astrocytes are preponderant glial elements, in contrast to the other "anamniotes" (and even to reptiles). We investigated stab wounds by the immunohistochemical detection of GFAP in turtles (Trachemys-formerly Pseudemys-scripta elegans), a skate (Raja clavata) and rays (Dasyatis akajei and Torpedo marmorata). Sharks (Scyliorhinus canicula) as ependymoglia-predominated chondrichthyans, and-for positive controls-rats were also studied. In the elasmobranchs, other astroglial markers: glutamine synthetase and S100 protein were also applied. Neither turtles nor elasmobranchs presented considerable astroglial reactions. Critically surveying the former reports on different vertebrates, these results complete the picture that typical post-lesion reactive gliosis is confined to mammals and birds. Analysis of the astroglial systems from phylogenetic perspective suggests that the capability of forming glial demarcation and scar formation evolved independently in mammals and birds. Predominance of astrocytes is a necessary condition but not sufficient for reactive gliosis. The intense glial reactivity of mammals and birds may be attributed to their complex cerebralization.

The asymmetry of 3H-imipramine binding may predict psychiatric illness.

The Bmax and Kd values for 3H-imipramine binding were measured in post-mortem human brains from drug-free selected psychiatric subject homicide victims (n = 15) and normal controls (n = 15). The two groups were comparable in age and gender. The number of imipramine binding sites (Bmax) in the frontal cortices of psychiatric subjects had significantly higher Bmax values in the left hemisphere than in the right hemisphere. Inversely, the number of imipramine binding sites (Bmax) in the frontal cortices of normal controls were significantly higher in the right brain than in the left brain. It was postulated that the inhibiting effect of central serotonin (5-HT) has weakened in psychiatric cases, therefore the change of presynaptic serotonergic activity might be associated with psychiatric illness in the left hemisphere of human brain.

Distribution of glial fibrillary acidic protein-immunopositive structures in the brain of the red-eared freshwater turtle (Pseudemys scripta elegans).

The distribution of glial fibrillary acidic protein (GFAP)-immunoreactivity is described in serial Vibratome sections of the turtle brain. The results are discussed in relation to our previous studies of rat and chicken brains. In the turtle brain, the distribution of GFAP-positive elements is rather evenly abundant as compared to that observed in the chicken and rat. The GFAP-positive structures are fibers of different length and orientation, but the stellate cells are not GFAP-positive. The basic systems is the radial ependymoglia, directed from the ventricles toward the outer surface of the brain. This system also contains some transverse and randomly oriented fibers. The cell bodies are not usually GFAP-positive. The large brain tracts could be recognized by their weak immunostaining, but gray matter nuclei could not be identified on the basis of immunostaining against GFAP. The layers of the optic tectum could be distinguished, as well as the gray and white matter of brain stem and spinal cord and the molecular and granular layers of the cerebellum. In the cerebellum, a fiber system resembling the Bergmann-fibers, a strong midline raphe and coarse transverse fibers could be observed. These latter fibers have no equivalent in other cerebella. Their perikarya proved also to be GFAP-positive, and seemed to be dividing in the adult turtle brain. We conclude that the appearance of GFAP-positive stellate cells had a great importance in the evolution of avian and mammalian brains strengthening the thicker brain walls and assisting in the formation of local differences of GFAP-immunoreactivity in different brain areas.

Distribution of glial fibrillary acidic protein-immunopositive structures in the developing brain of the turtle Mauremys leprosa.

This study is a continuation of the description of the glial fibrillary acidic protein (GFAP)-immunopositive structures in the adult turtle brain (Kálmán et al. 1994) and presents a comprehensive description of the development of these structures from the 20th embryonic day (E20) to the adult age. GFAP-immunopositive elements were first detected at E28 and by E34 the GFAP-immunopositivity was apparent throughout the brain, except the cerebellum. The appearance of GFAP seemed to be related to the end of cell migration and the formation of the thickened parts of the brain wall, such as the dorsal ventricular ridge. After hatching the pattern of the GFAP-immunopositivity differed from that in the adult only in minute details, except for the brain tracts in which GFAP-pattern was still changing due to myelination, and the molecular layer of the cerebellum in which a transverse fiber system appeared. The GFAP-positive elements belonged originally to the ependymoglia, but later the distortion due to the morphogenetic processes of branching and division changed the pattern almost beyond recognition. In some cases cell bodies--ependymal and non-ependymal--appeared to be GFAP-positive, but no astrocytes (i.e. stellate cells) were detected. The results are discussed in the light of previous observations on developing mammalian, avian and lizard brains.

Participation of periolivary neurons in the auditory brainstem circuitry. A Golgi, tracer and degeneration study.

Neurons in the periolivary areas of cat were described using Golgi methods and HRP labeling, and spineless neurons with distant projecting axons and spinous with local ramifying axons were distinguished. Spineless neurons fell into two classes, fusiform and multipolar cells characterised by the large number of terminals of various size, shape, vesicle content and membrane attachment articulating with them and both were identified as projection cells by retrograde tracer. They were, however, distinguished by the shape and orientation of their perikarya, the number, direction, branching pattern and composition of the presynaptic complement of their dendrites and their numerical occurrence and distribution among the periolivary areas. Spinous neurons had multipolar somata, wavy spinous dendrites spherically displayed and local, profusely ramifying axon arbor. Their somata and dendrites had few synaptic contacts with afferents, their axonal terminals escaped degeneration and since they failed to get labelled retrogradely from external sources they were considered as local interneurons. Based on morphological criteria and experimental results four types of axons were described. The large terminals with asymmetric membrane contacts and round vesicles took origin from the cochlear nuclei, and terminals of symmetrical membrane specialisation with pleomorphic vesicle content were traced from the inferior colliculus. Small profiles containing ovoid vesicles were considered as terminals of interneurons and the few, with round vesicles as local axoncollaterals.

Convergence of topographic projections to the inferior colliculus from the auditory subcollicular nuclei.

Light and electron microscope studies on experimental material were undertaken in order to identify the composition of sets of specific subcollicular afferents converging to distinct groups of neurons in the inferior colliculus and the morphological characteristics of their parent cells. Microinjections of the retrograde tracer HRP placed in gride-like distribution into the CNIC revealed topographical order and quantitative differences in the convergence of axon projections from specific regions of the VCN, DCN, MSO, LSO, VNLL and DNLL. Pilot studies indicated very low number of labelled neurons and without discernible topographic arrangement in the auditory brain-stem nuclei, when the microinjections were in or largely in the cortical or external nuclei of the inferior colliculus. Neurons occupying the ventromedial quadrant of CNIC receive converging contralateral input projections from the dorsal part of the DCN, dorsomedial half of the LSO, and DNLL as well as ipsilateral connections from the ventral part of the VNLL, DNLL and the dorsal half of the MSO. The set of converging afferents to neurons in the ventrolateral quadrant of CNIC arises from the contralateral part of the VCN, the DNLL and from the ipsilateral ventral part of the VNLL, dorsal part of the MSO and the dorsolateral half of the LSO. Projections to cells of the dorsomedial and dorsolateral quadrants are mirror images of those to the ventral ones across the transverse axis of the CNIC.

Neuron morphology and synaptic architecture in the medial superior olivary nucleus. Light- and electron microscope studies in the cat.

Dendritic arborization pattern, spatial and synaptic relations of various neuron types and the terminal distribution of afferent axons of various origin were studied in the medial superior olivary nucleus of the cat using Golgi, degeneration, electron microscope and horseradish peroxidase techniques. Three types of neurons clearly different in morphological features, distribution, neighbourhood relations, input and output characteristics were distinguished: (1) fusiform cells having specific dendritic orientations and arborization patterns and synaptic relations to various types of terminal axon arborizations (2) multipolar neurons with wavy dendrites bearing spine-like appendages, receiving relatively few synaptic contacts and having a locally arborizing axon, and (3) elongated marginal cells, largely restricted to the fibrous capsule of the nucleus. The fusiform and marginal neurons were identified by retrograde peroxidase labeling as the olivo-collicular projection cells. Ultrastructural analysis of normal and experimental material revealed the presence of four distinct kinds of axon terminals differing in size, synaptic vesicles type, relation to postsynaptic targets and in origin: (i) large terminals with multiple extended asymmetric synaptic membrane specializations and containing round, clear vesicles arise from the spherical cells of the ipsilateral anteroventral cochlear nucleus, (ii) most of the small axon terminal profiles - engaged in asymmetric synaptic contacts - originated from the trapezoid nucleus, (iii) terminal boutons containing pleomorphic vesicles belong to fibers descending from the ipsilateral multipolar neurons in the central nucleus of the inferior colliculus and from the nuclei of the lateral lemniscus while (iv) boutons containing exclusively ovoid vesicles and remaining intact after complete deafferentation of the nucleus were considered to be of local origin.

Types of neurons and synaptic relations in the lateral superior olive of the cat: normal structure and experimental observations.

Light and electron microscope studies on normal and experimental material in the lateral superior olive (LSO) of cat revealed the presence of three types of neurons: (i) fusiform cells characterized by the large number of terminals articulating with them and projecting to the nuclei of the lateral lemniscus (NLL) and central nucleus of the inferior colliculus (CNIC) (ii) marginal cells embedded in the neuropil of the fibrous capsule and sharing input and output characteristics with the fusiform neurons (iii) multipolar cells with spinous dendrites, local axonal spread and synaptic relation restricted to few afferents only. Four distinct types of axon terminals were distinguished on the basis of their size, vesicle content, membrane attachments, postsynaptic relations and origin. (i) Large terminals with asymmetrical membrane contacts and round vesicles (AR) were of ipsilateral cochlear nucleus origin and articulated predominantly with fusiform and marginal projection cells. (ii) The majority of small AR type terminals arose from the spherical cells of the ipsilateral nucleus of the trapezoid body (NTB). Their number was larger on the fusiform and marginal cells. (iii) Medium sized terminals of symmetrical membrane apposition and pleomorphic vesicles originated from the ipsilateral NLL and CNIC. Their quantitative distribution indicated preference for the multipolar cells. (iv) Profiles with symmetrical membrane contacts and flattened vesicles (SF) type were considered to be terminals of the spinous multipolar interneurons, thus local in origin.

Specific patterns of neuron arrangement and of synaptic articulation in the medial geniculate body.

Golgi and electron microscopic analysis of the known cellular layers in concentric shells of the ventro-lateral portion of the medial geniculate body revealed a flat grid of high density neuropil filling the space between the geniculocortical relay cells, forming essentially a single cell layer in each lamina. The "skeleton" of this neuropil grid is made up by the interdigitating dendritic tufts of the geniculocortical relay cells, joined together by a rich system of desmosomoid adhesion plaques. The "holes" of the "skeleton" are filled in by the multilobed dendritic appendages of Golgi type II interneurons and the grape-like terminals of the inferior collicular specific afferents. Additional axon terminals of other sources--terminals of descending corticogenicular fibers, axons of the Golgi type II interneurons and terminals of the initial collaterals of the geniculocortical relay cells--contribute only to a very insignificant fraction of neuropil volume. The Golgi type II interneurons are oriented in perpendicular direction to the cell layers so that they may bridge with their dendrites several successive layers. Although the general expression "synaptic glomeruli" used in other relay nuclei for this type of specific synaptic arrangement is hardly applicable to this grid-like neuropil, the essential synaptic articulation pattern of all thalamic relay nuclei is well maintained. The specific inferior collicular afferents are presynaptic to both relay cell dendrites and to the multilobed dendritic appendages of Golgi type II cells, which in turn are presynaptic to the same dendritic regions of the relay cells receiving the bulk of the specific afferents.

Types of interneurons and their participation in the neuronal network of the medial geniculate body.

Three different types of interneurons can be separated in the Golgi picture, and many of their details can be identified under the electron microscope, in the medial geniculate body (MGB) of the cat: (1) typical short axon Golgi II. cells of the thalamic type, (2) somewhat larger Golgi type II cells with medium range axon, and (3) spidery neurogliform short axon cells. The most distinctive features of the two first types (1) and (2) are their irregular drumstick shape appendages, increasing in number as well as in length and irregularity of their stalks towards the periphery of the dendrites. These appendages form the vast majority of synaptic profiles in the aggregations of synaptic neuropil (glomeruli) of the nuclei, and they are both presynaptic and postsynaptic by the usual standards applied for the evaluation of the polarity of synapses. The characteristic beaded dendrites of the (3) neurogliform cell type can be recognised particulary easily in the electron microscopic picture. They are both presynaptic and postsynaptic in structural polarity. All identified process profiles of interneurons contain flattened (F-type) or pleomorphic synaptic vesicles. Membrane contacts, in which the interneurons appear to be presynaptic are either of the symmetric (Gray type II) or of an intermediate type. The membrane contacts of postsynaptic portions of the interneurons are usually of the asymmetric type (Gray type I) and the presynaptic profiles contain round (R-type) vesicles. The larger one have been shown already earlier to be derived from specific sensory (inferior collicular) afferents, while many of the smaller ones could be identified in the present study as being derived from cortico-geniculate descending pathways, arising from the auditory areas. Some of the synaptic contacts of the interneurons are apparently derived from other interneurons, the presynaptic profiles being often equivocal or more likely of axonal origin (all interneurons have clear axons in the Golgi picture). The occurrence of three distinct types of interneurons--probably all of inhibitory nature--the complexity in synaptic arrangement, and more particularly in the dendritic linkage of numerous synaptic sites does not favour such simple explanations as surround inhibition by forward or by backward inhibition, but suggests more sophisticated modes of impulse processing in the MGB.

Does 3H-imipramine binding asymmetry indicate psychiatric illness?

We have accepted that serotonin is essentially an inhibitory neurotransmitter in the human brain, so we propose that it is precisely this inhibiting effect that has weakened in psychiatric cases. We have investigated the asymmetry of tritiated imipramine binding sites (Bmax) in the frontal cortices of homicide victims (n = 6) and controls (n = 6) who died of natural causes. Of these homicide victims examined in our experiment, five proved to have been psychiatric cases and one case had no psychiatric record. The two groups were comparable in age, gender and postmortem delay. The number of imipramine binding sites (Bmax) in the frontal cortices of controls was significantly higher in the right hemisphere than in the left hemisphere. But the homicide victims who were psychiatric cases had significantly higher (Bmax) values in the left hemisphere. While we only found higher Bmax values in the left hemisphere of homicide victims with mental diseases, our data may serve to prove the direct role of the serotonergic mechanism in the development of psychiatric cases.