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PubMedDate not supplied

[Progress in research on etiopathogenesis of schizophrenia in recent decades].

In this paper, a progress in research on etiopathogenesis of schizophrenia made in the recent decade was presented. Two main etiopathogenetic factors in this illness include genetic predisposition and brain damage in early period of life, leading to a disorder of brain development and lateralization, and to an increased susceptibility to stress. The use of new methods of genetic studies brought about a significant progress as to identification of relationship between schizophrenia and various changes within genotype. In the 1990s, many data have been obtained concerning possible brain damaging factors as well as the existence of structural and functional brain abnormalities in this illness. Impaired brain development in schizophrenia results in disturbances of neuronal connection in the cortical structures and in cortical-limbic transmission, what may underlie the appearance of psychopathological symptoms. New neuroleptic drugs introduced in the recent years show more complete therapeutic action against schizophrenic symptoms compared with drugs used so far. This may result from their broader influence on the pathogenetic processes of schizophrenia, which may be due, apart from their effect on dopaminergic system, also to their action on some elements of serotonergic neurotransmission.

Antipsychotic Agents↗
PubMed1998

Regeneration of cochlear efferent nerve terminals after gentamycin damage.

Chickens recover auditory function after hair cell loss caused by ototoxic drug damage or acoustic overstimulation, indicating that mechanisms exist to reestablish appropriate neuronal connections to regenerated hair cells. However, despite similar hair cell regeneration times, hearing recovery takes substantially longer after aminoglycoside than after sound damage. We have therefore begun examining damage and regeneration of efferent nerve terminals by immunolabeling whole-mount cochleae for differentially localized synaptic proteins and by visualizing the distribution of label with confocal microscopy. In undamaged cochleae, the synaptic proteins synapsin and syntaxin show similar distribution patterns corresponding to the large cup-like terminals on short hair cells. After gentamycin administration, these terminals are disrupted as hair cells are lost, leaving smaller, more numerous synapsin-reactive structures in the sensory epithelium. Syntaxin reactivity remains associated with the extruded hair cells, indicating that the presynaptic membrane is still attached to the postsynaptic site. In contrast, after sound damage, both synapsin and syntaxin reactivity are lost from the epithelium with extruded hair cells. As regenerated hair cells differentiate after gentamycin treatment, the synapsin labeling associated with cup-like efferent endings reappears but is not completely restored even after 60 d of recovery. Thus, efferent terminals are reestablished much more slowly than after sound damage (), consistent with the prolonged loss of hearing function. This in vivo model system allows comparison of axonal reconnection after either complete loss (sound damage) or partial disruption (gentamycin treatment) of axon terminals. Elucidating the differences in recovery between these injuries can provide insights into reinnervation mechanisms.

Animals↗
PubMed1998

Direct participation of starburst amacrine cells in spontaneous rhythmic activities in the developing mammalian retina.

Spontaneous, rhythmic waves of excitation in the developing mammalian retina play a critical role in the formation of precise neuronal connectivity in the visual system. However, it is not known what circuits in the retina are responsible for the production of these waves. Using patch-clamp recordings in the whole-mount neonatal rabbit retina, this study reports that the displaced starburst amacrine cell, a unique cholinergic interneuron in the ganglion cell layer of the retina, undergoes rhythmic bursts of membrane depolarization with a frequency and duration similar to those of spontaneous retinal waves. Simultaneous patch-clamp recordings from pairs of neighboring starburst and ganglion cells show that the rhythmic activity in starburst cells is closely correlated with that in ganglion cells, and that the excitation in both cell types is most likely driven by synaptic input. However, in contrast to ganglion cells, displaced starburst cells usually do not generate spontaneous somatic action potentials. Instead, they seem to use subthreshold potentials (at least at the soma) to mediate the rhythmic excitation. The results suggest that acetylcholine is likely released rhythmically in the developing retina. Thus, starburst amacrine cells form the first identified network of retinal interneurons that directly participate in spontaneous rhythmic activities in the developing retina.

Action Potentials↗
PubMed1998

Multivesicular release at single functional synaptic sites in cerebellar stellate and basket cells.

The purpose of the present work was to test the hypothesis that no more than one vesicle of transmitter can be liberated by an action potential at a single release site. Spontaneous and evoked IPSCs were recorded from interneurons in the molecular layer of cerebellar slices. Evoked IPSCs were obtained using either extracellular stimulation or paired recordings of presynaptic and postsynaptic neurons. Connections were identified as single-site synapses when evoked current amplitudes could be grouped into one peak that was well separated from the background noise. Peak amplitudes ranged from 30 to 298 pA. Reducing the release probability by lowering the external Ca2+ concentration or adding Cd2+ failed to reveal smaller quantal components. Some spontaneous IPSCs (1.4-2.4%) and IPSCs evoked at single-site synapses (2-6%) were followed within <5 msec by a secondary IPSC that could not be accounted for by random occurrence of background IPSCs. Nonlinear summation of closely timed events indicated that they involved activation of a common set of receptors and therefore that several vesicles could be released at the same release site by one action potential. An average receptor occupancy of 0.70 was calculated after single release events. At some single-site connections, two closely spaced amplitude peaks were resolved, presumably reflecting single and double vesicular release. Consistent with multivesicular release, kinetics of onset, decay, and latency were correlated to IPSC amplitude. We conclude that the one-site, one-vesicle hypothesis does not hold at interneuron-interneuron synapses.

Animals↗
PubMed1999

Reg1ulatory role and molecular interactions of a cell-surface heparan sulfate proteoglycan (N-syndecan) in hippocampal long-term potentiation.

The cellular mechanisms responsible for synaptic plasticity involve interactions between neurons and the extracellular matrix. Heparan sulfates (HSs) constitute a group of glycosaminoglycans that accumulate in the beta-amyloid deposits in Alzheimer's disease and influence the development of neuron-target contacts by interacting with other cell surface and matrix molecules. However, the contribution of HSs to brain function is unknown. We found that HSs play a crucial role in long-term potentiation (LTP), a finding that is consistent with the idea that converging molecular mechanisms are used in the development of neuron-target contacts and in activity-induced synaptic plasticity in adults. Enzymatic cleavage of HS by heparitinase as well as addition of soluble heparin-type carbohydrates prevented expression of LTP in response to 100 Hz/1 sec stimulation of Schaffer collaterals in rat hippocampal slices. A prominent carrier protein for the type of glycans implicated in LTP regulation in the adult hippocampus was identified as N-syndecan (syndecan-3), a transmembrane proteoglycan that was expressed at the processes of the CA1 pyramidal neurons in an activity-dependent manner. Addition of soluble N-syndecan into the CA1 dendritic area prevented tetanus-induced LTP. A major substrate of src-type kinases, cortactin (p80/85), and the tyrosine kinase fyn copurified with N-syndecan from hippocampus. Moreover, association of both cortactin and fyn to N-syndecan was rapidly increased after induction of LTP. N-syndecan may thus act as an important regulator in the activity-dependent modulation of neuronal connectivity by transmitting signals between extracellular heparin-binding factors and the fyn signaling pathway.

Animals↗
PubMed2002

Late-stage immature neocortical neurons reconstruct interhemispheric connections and form synaptic contacts with increased efficiency in adult mouse cortex undergoing targeted neurodegeneration.

In the neocortex, the effectiveness of potential cellular repopulation therapies for diseases involving neuronal loss may depend critically on whether newly incorporated cells can differentiate appropriately into precisely the right kind of neuron, re-establish precise long-distance connections, and reconstruct complex functional circuitry. Here, we test the hypothesis that increased efficiency of connectivity could be achieved if precursors could be more fully differentiated toward desired phenotypes. We compared embryonic neuroblasts and immature murine neurons subregionally dissected from either embryonic day 17 (E17) (Shin et al., 2000) or E19 primary somatosensory (S1) cortex and postnatal day 3 (P3) purified callosal projection neurons (CPNs) with regard to neurotransmitter and receptor phenotype and afferent synapse formation after transplantation into adult mouse S1 cortex undergoing targeted apoptotic degeneration of layer II/III and V CPNs. Two weeks after transplantation, neurons from all developmental stages were found dispersed within layers II/III and V, many with morphological features typical of large pyramidal neurons. Retrograde labeling with FluoroGold revealed that 42 +/- 2% of transplanted E19 immature S1 neurons formed connections with the contralateral S1 cortex by 12 weeks after transplantation, compared with 23 +/- 7% of E17 neurons. A greater percentage of E19-derived neurons received synapses (77 +/- 1%) compared with E17-derived neurons (67 +/- 2%). Similar percentages of both E17 and E19 donor-derived neurons expressed neurotransmitters and receptors [glutamate, aspartate, GABA, GABA receptor (GABA-R), NMDA-R, AMPA-R, and kainate-R] appropriate for endogenous adult CPNs progressively over a period of 2-12 weeks after transplantation. Although P3 fluorescence-activated cell sorting-purified neurons also expressed these mature phenotypic markers after transplantation, their survival in vivo was poor. We conclude that later-stage and region-specific immature neurons develop a mature CPN phenotype and make appropriate connections with recipient circuitry with increased efficiency. However, at postnatal stages of development, limitations in survival outweigh this increased efficiency. These results suggest that efforts to direct the differentiation of earlier precursors precisely along specific desired neuronal lineages could potentially make possible the highly efficient reconstruction of complex neocortical and other CNS circuitry.

Animals↗
PubMed2006

A mathematical framework for inferring connectivity in probabilistic neuronal networks.

We describe an approach for determining causal connections among nodes of a probabilistic network even when many nodes remain unobservable. The unobservable nodes introduce ambiguity into the estimate of the causal structure. However, in some experimental contexts, such as those commonly used in neuroscience, this ambiguity is present even without unobservable nodes. The analysis is presented in terms of a point process model of a neuronal network, though the approach can be generalized to other contexts. The analysis depends on the existence of a model that captures the relationship between nodal activity and a set of measurable external variables. The mathematical framework is sufficiently general to allow a large class of such models. The results are modestly robust to deviations from model assumptions, though additional validation methods are needed to assess the success of the results.

Algorithms↗
PubMed1992

Connectivity of chemosensory neurons is controlled by the gene poxn in Drosophila.

The function of the nervous system depends on the formation of a net of appropriate connections, but little is known of the genetic program underlying this process. In Drosophila two genes that specify different types of sense organs have been identified: cut (ct), which specifies the formation of external sense organs as opposed to chordotonal organs, and pox-neuro (poxn), which specifies the formation of poly-innervated (chemosensory) organs as opposed to mono-innervated (mechanosensory) organs. Whether these genes are also involved in specifying the connectivity of the corresponding neurons is not known. The larval sense organs are unsuitable for analysis of the axonal pathway and connections and so we have investigated the effect of poxn on the adult. Here we show that overexpression of poxn induces the morphological transformation of mechanosensory into chemosensory bristles on the legs and that the neurons innervating the morphologically transformed bristles follow pathways and establish connections that are appropriate for chemosensory bristles.

Animals↗
PubMed1984

[Ultrastructure of sensorimotor cortex neurons and interneuronal connections in the progeny of alcoholized rats].

The sensorimotor cortex of the alcoholized rat progeny showed the signs of the delayed ultrastructural development of neurons and interneuronal connections and their dystrophic changes, particularly in 21-day-old experimental rats. Thirty-day-old animals demonstrated pronounced reparative alterations. But in spite of this fact the ultrastructure of cortical neurons, particularly of dendrites was not completely restored.

Animals↗
PubMed2006

Phase-model analysis of coupled neuronal oscillators with multiple connections.

Synchronization of the coupled neuronal oscillators with multiple connections of different coupling nature is analyzed using the phase-model reduction method. Each coupling connection contributes to the dynamic behavior of the system in a complex nonlinear fashion. In the phase-model scheme, the contribution of the individual connections can be separated in terms of the effective coupling functions associated with each connection and a linear superposition of them provides the total effective coupling of the coupled system. The case of multiple connections with various conduction time delays is also examined, which is shown to be capable of promoting synchronization over an ensemble of spatially distributed neuronal oscillators in an efficient way.

Hippocampus↗
PubMed2004

The distribution of immunoreactivity for intracellular androgen receptors in the cerebral cortex of hormonally intact adult male and female rats: localization in pyramidal neurons making corticocortical connections.

Gonadal hormones are known to broadly influence cortical information processing. Findings from this study in rats suggest that for androgens, this influence may include stimulation of underlying corticocortical connections. First, immunoreactivity for intracellular androgen receptors, while present in all regions and layers examined, was found to be particularly abundant in sensory and motor regions, and within these, within their major pyramidal cell layers, i.e. layers II/III and V/VI. Double labeling immunocytochemical studies for androgen receptors and for neuron-specific markers then confirmed that the majority of receptor-bearing cortical cells were pyramidal neurons. Finally, combined analyses of cortical receptor immunoreactivity and retrograde labeling produced by tracer injections made in specific subcortical (caudate, nucleus accumbens, superior colliculus, thalamus) areas yielded only isolated examples of receptor/tracer overlap. However, injections made within the cortex itself (sensory, motor, associational areas) retrogradely labeled cortical cells some 50% or more - especially within injected hemispheres, were receptor-immunoreactive. Thus, the regional, laminar, and cellular distributions of immunoreactivity in the rat cerebrum largely identify pyramidal neurons with connectional signatures aligning intracellular androgen receptors with the local, associational, and to a lesser degree, callosal circuits that interlink territories of the cortical mantle and play key roles in cortical information processing.

Animals↗
PubMed1979

Organization of trigeminothalamic tracts and other thalamic afferent systems of the brainstem in the rat: presence of gelatinosa neurons with thalamic connections.

Thalamic projections from trigeminal and certain other nuclei of the brainstem of the rat have been investigated using the technique of retrograde transport of horseradish peroxidase (HRP). The pattern of trigeminothalamic projections is very specifically related to the individual subnuclei of the complex. The Main Sensory Nucleus (MSN) provides profuse cross connections to the ventrobasal thalamus (VB); these arise exclusively from medium and small-sized neurons, but never from the large cells. In addition to these crossed connections, a small ipsilateral dorsal trigeminothalamic tract arises from the dorsal third of the most rostral part of the MSN; this is the only ipsilateral connection to VB found in the trigeminal complex. Subnucleus Oralis has no projections to the thalamus; it is suggested that it may be concerned primarily with reflex activation of the facial nucleus, with which it is co-extensive in the rostro-caudal axis. Subnucleus Interpolaris has a well-defined crossed projection of moderate size which arises from the large, medium and some of the small neurons. Subnucleus Caudalis has a sparse output to the thalamus and differs in its projections from rostral to caudal. At the most rostral level, all layers (marginal, transitional gelatinosa and magnocellularis) contain neurons which project to the thalamus; particularly conspicuous in this respect are the marginal neurons, most of which are strongly labelled. The presence of gelatinosa neurons projecting to the thalamus emphasizes a point made in earlier reports, that these neurons do not form an homogeneous population. At caudal levels, the marginal neurons are the major source of thalamic projections, while connections to the thalamus form deeper lying neurons are infrequent. With a single exception, the medullary reticular nuclei contained no neurons with thalamic connections; a small number of reticulo-thalamic neurons were found in the ventral pontine area. Marked labelling of the medial cuneate nucleus and moderate labelling of the gracilis and lateral cuneate nuclei occurred contralaterally to the injection site. A small numebr of medial cuneate and gracile neurons project to the ipsilateral thalamus. Projections from the solitary nucleus were always ipsialteral. The boundaries of individual subnuclei of the lateral sensory trigeminal complex in the rat have been redefined on the basis of cytological criteria; these are in good accord with the corresponding thalamic projection patterns.

Animals↗
PubMed1991

Immunoelectron microscopic analysis of the synaptic connectivity of serotoninergic neurons grafted to the 5,7-dihydroxytryptamine-lesioned rat spinal cord.

The connections between the host and 5-hydroxytryptamine-containing neurons grafted to the spinal cord have been analysed using electron microscopic immunohistochemistry. Adult rats with 5,7-dihydroxytryptamine lesions of the brain and spinal cord received implants of embryonic medullary raphé neurons at three sites in the spinal cord. Eight to 10 months after grafting, the transplanted 5-hydroxytryptamine-positive neurons had formed extensive and complex contacts with spines, dendrites, perikarya and vesicle-containing structures in both the dorsal and ventral horns. Reinnervation of laminae IV-VI was less rich. In the graft itself, connections were also made between non-immunoreactive varicosities and 5-hydroxytryptamine-containing dendrites, and somata, but the exact origin of the afferents was not determined. Outside the implant site, no obvious synaptic junctions onto grafted 5-hydroxytryptamine-immunoreactive boutons were obvious, although labelled and unlabelled varicosities were often in close apposition. Synaptic junctions in the dorsal horn were predominantly symmetric, with the presynaptic varicosity containing mostly small agranular vesicles. By contrast, in the ventral horn most junctions were asymmetric, while the presynaptic element contained both small agranular and large dense-core vesicles. The results demonstrate that the types of synaptic contacts formed between the grafted 5-hydroxytryptamine neurons and the host spinal cord are remarkably similar to those found in intact spinal cord. In addition, the division of morphological differences that exists between 5-hydroxytryptamine-containing boutons in the normal dorsal vs ventral horns is also apparent in the transplanted animals. Finally, there appear to be present several anatomical substrates for the regulation by the host of 5-hydroxytryptamine output from the grafted neurons.

5,7-Dihydroxytryptamine↗
PubMed2003

Ectopic sympathetic preganglionic neurons maintain proper connectivity in the reeler mutant mouse.

The location of sympathetic preganglionic neurons (SPN) in the spinal cord of the reeler mouse mutant is abnormal. Instead of their normal location in the intermediolateral column, the majority of SPN in the reeler cluster around the central canal. To determine whether ectopically located SPN in the reeler form appropriate synaptic connections with their pre- and postsynaptic partners, we examined 1). whether the axons of descending neural pathways that normally terminate on SPN follow them to their ectopic location, and 2). whether the central autonomic neural circuit that controls sympathetic output to the kidney is organized normally in the reeler. Using antibodies against tyrosine hydroxylase, serotonin, neuropeptide Y, substance P and calcitonin gene-related peptide as markers for adrenergic, serotonergic and peptidergic terminals, we found that axons which normally innervate SPN follow these neurons to their ectopic spinal location in the reeler. Injection of pseudorabies virus into the kidney of wild type and reeler mutant mice revealed similar patterns of renal sympathetic and pre-sympathetic control circuits in the spinal cord, brainstem and forebrain. These results indicate that the presynaptic inputs and postsynaptic targets of SPN in the reeler are normal, despite the ectopic spinal location of their cell bodies.

Animals↗
PubMed1995

Immunohistochemical properties and spinal connections of pelvic autonomic neurons that innervate the rat prostate gland.

Autonomic innervation of the prostate gland supplies the acini, and non-vascular and vascular smooth muscle. The activity of each of these tissues is enhanced by sympathetic outflow, whereas the role of the parasympathetic nervous system in this organ is unclear. In the present study, a range of methods was applied in rats to determine the location of autonomic neurons supplying this gland, the immunohistochemical properties of these neurons, the spinal connections made with the postganglionic pathways and the distribution of various axon types within the gland. Injection of the retrograde tracer, FluoroGold, into the ventral gland visualised neurons within the major pelvic ganglion and sympathetic chain. Fluorescence immunohistochemical studies on the labelled pelvic neurons showed that most were nonadrenergic (also containing neuropeptide Y, NPY), the others being non-noradrenergic and containing either vasoactive intestinal peptide (VIP) or NPY. Sympathetic dye-labelled neurons were identified by the presence of varicose nerve terminals stained for synaptophysin on their somata following lesion of sacral inputs. Parasympathetic innervation of dye-labelled neurons was identified by continued innervation after hypogastric nerve lesion. Most noradrenergic prostate-projecting neurons were sympathetic, as were many of the non-noradrenergic VIP neurons. Parasympathetic prostate-projecting neurons were largely non-noradrenergic and contained either VIP or NPY. All substances found in retrogradely labelled somata were located in axons within the prostate gland but had slightly different patterns of distribution. The studies have shown that there are a significant number of non-noradrenergic sympathetic prostate-projecting neurons, which contain VIP.

Animals↗
PubMed2000

Connectivity of ectopic neurons in the molecular layer of the somatosensory cortex in autoimmune mice.

Approximately 50% of New Zealand Black mice (NZB/BINJ) and 80% of NXSM-D/EiJ mice prenatally develop neocortical layer I ectopias, mostly in somatosensory cortices. These cortical anomalies are similar to those seen in the brains of individuals with dyslexia. Neurofilament staining revealed a radial column of tightly packed fiber bundles in the layers underlying ectopias. This suggested that the connectivity of the ectopic neurons was aberrant. The present study used the tracers 1,1'-dioctadecyl- 3,3,3',3'-tetramethylindo- carbocyanine perchlorate (DiI) and biotinylated dextran amine (BDA) to more thoroughly explore the cortical and thalamic connectivity of the ectopias. DiI placement into ectopias again revealed a distinct bundle of fibers extending from the ectopic neurons to the deep cortical layers. This bundle split in the white matter with some fibers traveling to the corpus callosum and others to the internal capsule. Thalamic connections were concentrated in the ventrobasal com- plex (VB) and posterior thalamic nucleus group (Po). Injections of BDA into VB revealed reciprocal connections between VB and the ectopic cortical neurons. Ipsilateral corticocortical projections were seen between ectopias in primary somatosensory and motor and secondary somatosensory cortices, but no contralateral connections of the ectopic neurons were seen. These findings confirm the notion that layer I ectopias are anomalously connected by comparison to neurons in homologous cortex, which may underlie widespread dysfunction of brains containing ectopias.

Animals↗
PubMedDate not supplied

Mono- and polysynaptic connections between identified neurons in the system of the passive avoidance reflex of the snail.

The structure of the synaptic connections between identified sensory and giant command neurons of the parietal ganglia of the snail is examined. It is shown that the excitatory postsynaptic potential arising in the giant neuron in response to the generation of a single action potential in the presynaptic neuron consists of several monosynaptic components and may include polysynaptic components. It is hypothesized that monosynaptic components of the elementary excitatory postsynaptic potential that differ in the duration of the latent period and the dynamics of habituation may be associated with the activation of synaptic buttons on axon terminals of varying length.

Action Potentials↗
PubMed2003

Rearrangement of synaptic connections with inhibitory neurons in developing mouse visual cortex.

Cortical inhibition is determined in part by the organization of synaptic inputs to gamma-aminobutyric acidergic (GABAergic) neurons. In adult rat visual cortex, feedforward (FF) and feedback (FB) connections that link lower with higher areas provide approximately 10% of inputs to parvalbumin (PV)-expressing GABAergic neurons and approximately 90% to non-GABAergic cells (Gonchar and Burkhalter [1999] J. Comp. Neurol. 406:346-360). Although the proportions of these targets are similar in both pathways, FF synapses prefer larger PV dendrites than FB synapses, which may result in stronger inhibition in the FF than in the FB pathway (Gonchar and Burkhalter [1999] J. Comp. Neurol. 406:346-360). To determine when during postnatal (P) development FF and FB inputs to PV and non-PV neurons acquire mature proportions, and whether the pathway-specific distributions of FF and FB inputs to PV dendrites develop from a similar pattern, we studied FF and FB connections between area 17 and the higher order lateromedial area (LM) in visual cortex of P15-42 mice. We found that the innervation ratio of PV and non-PV neurons is mature at P15. Furthermore, the size distributions of PV dendrites contacted by FF and FB synapses were similar at P15 but changed during the third to sixth postnatal weeks so that, by P36-42, FF inputs preferred thick dendrites and FB synapses favored thin PV dendrites. These results suggest that distinct FF and FB circuits develop after eye opening by rearranging the distribution of excitatory synaptic inputs on the dendritic tree of PV neurons. The purpose of this transformation may be to adjust differentially the strengths of inhibition in FF and FB circuits.

Aging↗