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Mechanisms underlying olfactory neuronal connectivity in Drosophila-the atonal lineage organizes the periphery while sensory neurons and glia pattern the olfactory lobe.

Patterning of the antennal lobe of adult Drosophila occurs through a complex interaction between sensory neurons, glia, and central neurons of larval and adult origin. Neurons from the olfactory sense organs are organized into distinct fascicles lined by glial cells. The glia originate from one of the three types of sensory lineages-specified by the proneural gene atonal. Gain-of-function as well as loss-of-function analysis validates a role for cells of the Atonal lineage in the ordered fasciculation of sensory neurons. Upon entry of the antennal nerve to central regions, sensory neurons at first remain closely associated with central glia which lie around the periphery of the lobe anlage. Coincident with the arrival of sensory neurons into the brain, glial precursors undergo mitosis and neural precursors expressing Dachshund appear around the lobe. Sensory neurons and glial cells project into the lobe at around the same time and are likely to coordinate the correct localization of different glomeruli. The influence of sensory neurons on the development of the olfactory lobe could serve to match and lock peripheral and central properties important for the generation of olfactory behavior.

Animals↗

Neuronal connections, cell formation and cell migration in the perinatal human hippocampal dentate gyrus.

Jean Piaget's "stage theory" suggests that cognitive development proceeds in discrete steps, among which the first is the sensorimotor period that occupies the first two years. In recent years it became clear that an intact and mature hippocampus is necessary for memory formation both in experimental animals and in human. In the present experiments the perinatal morphological development of the human hippocampus was studied to describe structural changes that may correlate with the developmental changes of intellectual growth. Our results suggest that cell formation in the human hippocampus terminates several weeks before birth, but immature cells migrate to their final positions through the first six postnatal months. The newborn hippocampus contains all cell types and cell layers that are characteristic for the adult hippocampus. However, changes of the light microscopic features of the postsynaptic target neurons of hippocampal granule cells indicate that connections between granule cells and their target neurons are immature at birth and develop through an extended period of time that may last for three years. Since this neuronal connection is the first link in the chain of the main hippocampal synaptic circuitry, it may be suggested that human hippocampus is functionally impaired at birth. This period of light microscopic morphological maturation correlates well with the time period of Piaget's first stage of cognitive development. It can also be suggested that the prolonged postnatal development of some neuronal circuitries in the human hippocampus may be responsible for the psychological phenomenon of "infantile amnesia", that is the lack of memory traces from the early postnatal period.

Adolescent↗

[Contour of auto- and cross-correlation histograms of the spike flows of monosynaptically connected neurons].

By methods of neuronal interaction modelling--biomathematical (computer controlled experiment on molluscs neurones) and mathematical--in wide physiological ranges of parameters values, characterizing properties and conditions of neurones and synapses functioning, the forms were studied of auto- and cross-correlation histograms of impulse flows of neurones at forward and backward monosynaptic connections between them. Specific form is established of cross-correlation histogram of impulse flows of interconnected neurones in conditions typical of CNS of mammals, when the neurones are subjected to intensive random afferent synaptic bombardment and do not reveal any pace-maker properties. It is also shown that random afferent synaptic bombardment prevents the appearance of excitation reverberation in closed neuronal circuits.

Action Potentials↗

Axon pruning: an essential step underlying the developmental plasticity of neuronal connections.

Regressive events play a key role in modifying neural connectivity in early development. An important regressive event is the pruning of neuronal processes. Pruning is a strategy often used to selectively remove exuberant neuronal branches and connections in the immature nervous system to ensure the proper formation of functional circuitry. In the following review, we discuss our present understanding of the cellular and molecular mechanisms that regulate the pruning of axons during neuronal development as well as in neurological diseases. The evidence suggests that there are several similarities between the mechanisms that are involved in developmental axon pruning and axon elimination in disease. In summary, these findings provide researchers with a unique perspective on how developmental plasticity is achieved and how to develop strategies to treat complex neurological diseases.

Animals↗

Interanalyzer two-way neuronal connections during alimentary conditioning in cats.

Milk conditioned reflexes to low frequency electrostimulation of optic tracts was examined in four cats. Multineuronal activity from visual and sensorimotor cortical regions was recorded under conditions of chronic implantation. Intra- and interanalyzer interneuronal connections were statistically analyzed by constructing crosscorrelograms. The comparison of the results of interneuronal interaction in untrained and trained animals showed an increase of one-way and two-way connections both of intra- and interanalyzer types. Neurons characterized by intermediate amplitude spike, more than other neurons, changed their network properties and were enriched by incoming and outgoing connections in both visual and sensorimotor cortex of the trained animals. An increase in the total number of interneuronal connections after acquisition was due to an increase of connections from the sensorimotor to the visual analyzer.

Animals↗

Receptive-field properties and neuronal connectivity in striate and parastriate cortex of contour-deprived cats.

An attempt was made to relate the alterations of cortical receptive fields as they result from binocular visual deprivation to changes in afferent, intrinsic, and efferent connections of the striate and parastriate cortex. The experiments were performed in cats aged at least 1 jr with their eyelids sutured closed from birth. The results of the receptive-field analysis in A17 confirmed the reduction of light-responsive cells, the occasional incongruity of receptive-field properties in the two eyes, and to some extent also the loss of orientation and direction selectivity as reported previously. Other properties common to numerous deprived receptive fields were the lack of sharp inhibitory sidebands and the sometimes exceedingly large size of the receptive fields. Qualitatively as well as quantitatively, similar alterations were observed in area 18. A rather high percentage of cells in both areas had, however, preserved at least some orientation preference, and a few receptive fields had tuning properties comparable to those in normal cats. The ability of area 18 cells in normal cats to respond to much higher stimulus velocities than area 17 cells was not influenced by deprivation. The results obtained with electrical stimulation suggest two main deprivation effects: 1) A marked decrease in the safety factor of retinothalamic and thalamocortical transmission. 2) A clear decrease in efficiency of intracortical inhibition. But the electrical stimulation data also show that none of the basic principles of afferent, intrinsic, and efferent connectivity is lost or changed by deprivation. The conduction velocities in the subcortical afferents and the differentiation of the afferents to areas 17 and 18 into slow- and fast-conducting projection systems remain unaltered. Intrinsic excitatory connections remain functional; this is also true for the disynaptic inhibitory pathways activated preferentially by the fast-conducting thalamocortical projection. The laminar distribution of cells with monosynaptic versus polsynaptic excitatory connections is similar to that in normal cats. Neurons with corticofugal axons remain functionally connected and show the same connectivity pattern as those in normal cats. The nonspecific activation system from the mesencephalic reticular formation also remains functioning both at the thalamic and the cortical level. We conclude from these and several other observations that most, if not all, afferent, intrinsic, and efferent connections of areas 17 and 18 are specified from birth and depend only little on visual experience. This predetermined structural plan, however, allows for some freedom in the domain of orientation tuning, binocular correspondence, and retinotopy which is specified only when visual experience is possible.

Animals↗

Brain grafts can restore irradiation-damaged neuronal connections in newborn rats.

Immature rat brain tissue grafted to the brain of other immature and adult rats can survive and establish nerve connections with the host brains. In addition to facilitating the study of factors involved in the formation of central neural connections, brain grafts may also be used to substitute damaged or maldeveloped neurones. With exceptions in the visual system, the restoration of specific central neural connections has to date involved grafts of cholinergic and monoaminergic neurones, which have good regenerative capacity. In the present study, rat hippocampal neurones were damaged by neonatal X-ray irradiation and replaced by transplantation of normal, developing neurones of the same type. The grafted neurones (dentate granule cells) are not cholinergic or monoaminergic, but when appropriately located in the host hippocampal region they established specific and highly ordered afferent and efferent connections with the damaged host brain. Moreover, simultaneous demonstration of afferent and efferent transplant pathways showed that serial host-transplant-host connections had formed, restoring the normal neuronal circuitry initially disrupted by the irradiation.

Animals↗

Intrinsic determinants of synaptic phenotype: an experimental study of abducens internuclear neurons connecting with anomalous targets.

The present experiments investigate the role of postsynaptic neurons in the morphological differentiation of presynaptic terminals that are formed de novo in the adult CNS. Abducens internuclear neurons in the adult cat were chosen as the experimental model. These neurons project onto the contralateral medial rectus motoneurons of the oculomotor nucleus. Abducens internuclear axon terminals were identified by their anterograde labeling with biocytin and analyzed at the electron microscopic level. To promote the formation of new synapses, two different experimental approaches were used. First, after the selective ablation of medial rectus motoneurons with ricin, abducens internuclear neurons reinnervated the neighboring oculomotor internuclear neurons. Second, after axotomy followed by embryonic cerebellar grafting, abducens internuclear axons invaded the implanted tissue and established synaptic connections in both the molecular and granule cell layer. Boutons contacting the oculomotor internuclear neurons developed ultrastructural characteristics that resembled the control synapses on medial rectus motoneurons. In the grafted cerebellar tissue, abducens internuclear axons and terminals did not resemble climbing or mossy fibers but showed similarities with control boutons. However, labeled boutons analyzed in the granule cell layer established a higher number of synaptic contacts than controls. This could reflect a trend towards the mossy fiber phenotype, although labeled boutons significantly differed in every measured parameter with the mossy fiber rosettes found in the graft. We conclude that at least for the abducens internuclear neurons, the ultrastructural differentiation of axon terminals reinnervating novel targets in the adult brain seems to be mainly under intrinsic control, with little influence by postsynaptic cells.

Abducens Nerve↗

When should we expect prenatally damaged human brains to have abnormal neuronal connections?

Abnormal function in prenatally damaged brains may occur as the result of loss of neuronal an/or glial elements, abnormal morphology of neurons, or abnormal and inappropriate connections. By abnormal connection I mean projections from a given nucleus to a nucleus or cortical region in the brain which does not normally receive such a projection. In the present paper it is proposed that focal brain damage, i.e. that damage involving circumscribed regions of the developing brain on one side of the body, is more likely to induce abnormal connections, than diffuse brain damage, affecting most of the brain bilaterally. This proposition is based on the available evidence from animal studies, albeit scanty, and is presented as a working hypothesis for future studies of human congenital brain damage.

Animals↗

Neuronal connectivity: bis repetita placent.

The mechanism that allows a sensory neuron to extend its terminal branches along the appropriate fascicle within the CNS turns out to be the same as that which positioned the fascicle earlier on, and the gene that controls this position is the same as that which determined the neuron's identity.

Animals↗

Cross-correlation analysis of neuron connections in the cerebellum of conscious rabbits.

Cross-interval and cross-correlation analysis of neuron activity was used to study cell interactions in the cerebellar vermis of conscious rabbits. The cross-correlation method, based on post-synaptic potentials (PSP) from one member of a pair of neurons, supplements the cross-interval analysis used for evaluating the interactions of neurons in terms of action potentials. A total of 16 neuron pairs were analyzed, in which the activity of one neuron was recorded intracellularly and that of the other extra- or intracellularly. Interactions were observed in 10 pairs. Most pairs showed inhibitory interactions. Pairs with inhibitory interactions included those in which the activity of one or both neurons contained complex spikes. Also of interest was the analysis of connections in which influences were excitatory in one direction and inhibitory in the other. In these cases, neuron discharges were invariably simple spikes. Variability and plasticity in the output signals of Purkinje cells were greater than the variability and plasticity of the common inputs to Purkinje cells.

Action Potentials↗

Alterations of neuronal connectivity in area CA1 of hippocampal slices from temporal lobe epilepsy patients and from pilocarpine-treated epileptic rats.

PURPOSE: Neuronal network reorganization might be involved in epileptogenesis in human and rat limbic epilepsy. Apart from aberrant mossy fiber sprouting, a more widespread fiber rearrangement in the hippocampal formation might occur. Therefore, we studied sprouting in area CA1 because this region is most affected in human temporal lobe epilepsy. METHODS: In slices from hippocampi of patients operated on for temporal lobe epilepsy (n = 134), from pilocarpine-treated rats (n = 74), and from control rats (n = 15), viable neurons were labeled with fluorescent dextran amines. RESULTS: In human hippocampi as well as in pilocarpine-treated rats, the degree of nerve cell loss varied. In 67 of 134 slices from human specimens with distinct Ammon's horn sclerosis and in 23 of 74 slices from pilocarpine-treated rats, a severe shrunken area CA1 presented with a similar picture: few damaged neurons were labeled, and aberrant fiber connections were not visible. This was in contrast to human resected hippocampi and hippocampi from pilocarpine-treated rats with no or moderate loss of neurons. In these cases, pyramidal cells remote from the injection site were labeled (human tissue, n = 59 of 134; pilocarpine-treated rats, n = 39 of 74). In human resected hippocampi without obvious pathology and in control animals, no pyramidal neurons were labeled apart from the injection site. CONCLUSIONS: Axon collaterals of CA1 pyramidal cells are increased in human temporal lobe epilepsy and in pilocarpine-treated rats. Adjacent CA1 pyramidal cells project via aberrant collaterals to the stratum pyramidale and the stratum radiatum of area CA1. This network reorganization can contribute to hyperexcitability via increased backward excitation.

Animals↗

bendless, a Drosophila gene affecting neuronal connectivity, encodes a ubiquitin-conjugating enzyme homolog.

The Drosophila bendless (ben) gene was originally isolated as a mutation affecting the escape jump response. This behavioral defect was ascribed to a single lesion affecting the connectivity between the giant fiber and the tergotrochanter motor neuron. A closer examination of the ben phenotype suggests that ben activity is broader and affects a variety of other neurons including photoreceptor cells and their axons. Mosaic analysis indicates that the focus of ben activity is presynaptic. We have cloned the ben gene through a chromosomal walk and show that it is homologous to a class of ubiquitin-conjugating enzymes. The major role of ubiquitination in the protein degradative pathway suggests that ben regulates neural developmental processes such as growth cone guidance by targeting specific proteins for degradation.

Amino Acid Sequence↗

Electrophysiological evidence for a direct neuronal connection from the motor cortex to the parietal association cortex of the cat.

Neuronal responses of the parietal association cortex to motor cortex stimulation were studied intracellularly in anaesthetized cats. Antidromic responses and monosynaptic excitatory postsynaptic potentials (EPSPs) of ipsilateral anterior suprasylvian and lateral gyri neurons have been established. Oligo- and polysynaptic EPSPs were also recorded. Some cells reacted with both antidromic and orthodromic excitation. It is concluded that, besides the well-known parietal-to-motor cortex projection, there is also a reciprocal link from the motor cortex back to the parietal association cortex.

Animals↗

Dynamics of spiking neurons connected by both inhibitory and electrical coupling.

We study the dynamics of a pair of intrinsically oscillating leaky integrate-and-fire neurons (identical and noise-free) connected by combinations of electrical and inhibitory coupling. We use the theory of weakly coupled oscillators to examine how synchronization patterns are influenced by cellular properties (intrinsic frequency and the strength of spikes) and coupling parameters (speed of synapses and coupling strengths). We find that, when inhibitory synapses are fast and the electrotonic effect of the suprathreshold portion of the spike is large, increasing the strength of weak electrical coupling promotes synchrony. Conversely, when inhibitory synapses are slow and the electrotonic effect of the suprathreshold portion of the spike is small, increasing the strength of weak electrical coupling promotes antisynchrony (see Fig. 10). Furthermore, our results indicate that, given a fixed total coupling strength, either electrical coupling alone or inhibition alone is better at enhancing neural synchrony than a combination of electrical and inhibitory coupling. We also show that these results extend to moderate coupling strengths.

Action Potentials↗

The intracortical neuronal connectivity subserving focal epileptiform activity in rat neocortex.

In the anaesthetized rat, regions of the somatosensory cortex have been subpially isolated, leaving intact the cortical blood supply and the connectivity via the white matter. Application of penicillin or strychnine into layer IV of intact cortex resulted in enhancement of amplitude and prolongation of evoked potentials together with the appearance of spontaneous epileptiform discharges. Within a partially isolated region of cortex, spontaneous and evoked potentials occurred as in normal cortex, but application of convulsant drug resulted in no changes in evoked potentials and in no spontaneous spiking. With incisions for which the surface profile measured 0.9 x 0.9 mm, full-depth isolation resulted in interruption of the propensity for epilepsy, whereas half-depth incisions left epileptic manifestations unimpaired. With the surface profile measuring 0.5 x 0.5 mm, half-depth isolation was sufficient to prevent epileptic activity. Results from isolated regions of various geometries and sizes indicated that the ability of cortical neurones to generate epileptic activity depends on the amount of connectivity with surrounding cortex. The propensity of cortex to become epileptic is thus a mass action effect and the 'epileptic neuronal aggregate' is operationally different from anatomically based modular organizations such as thalamo-cortical or cortico-cortical columns. In the small barrel field of the somatosensory cortex, partial isolations that prevented the appearance of spontaneous epileptiform spiking contained many barrels, indicating that a single thalamo-cortical module contains insufficient inherent lateral connectivity to support epileptiform activity. Theoretical considerations indicated that the excitability of a neurone depends both on its monosynaptic connections with other neurones and on the connectivity of these latter with neurones further afield. The interruption of epileptiform activity by partial isolation could be mimicked by a computer model in which connectivity was mediated via short synaptic paths. The model exhibited self-sustaining synchronized neural activity that could be prevented by interruption solely of polysynaptic paths.

Animals↗

Neural analogue of long-term sensitization training produces long-term (24 and 48 h) facilitation of the sensory-to-motor neuron connection in Aplysia.

1. An in vitro analogue of long-term sensitization training was used to gain insights into the mechanisms and time course of the memory for long-term sensitization in Aplysia. The analogue, consisting of four blocks of shocks, was delivered to peripheral nerves of the isolated pleural-pedal ganglia, which contain the sensory neurons and motor neurons that mediate the tail withdrawal reflex. 2. Long-term facilitation of the connections between the sensory neurons and motor neurons was produced by the conjoint stimulation of two peripheral nerves, P8 and P9. Long-term facilitation, however, was not observed after conjoint stimulation of three nerves, P7, P8, and P9. 3. The preparation was viable and stable (no changes in the amplitudes of excitatory postsynaptic potentials (EPSPs) and membrane properties in controls) for at least 48 h. Moreover, the long-term facilitation persisted for at least 48 h. 4. We observed no significant long-term changes in the resting membrane potentials of the sensory and motor neurons or in the input resistance of the motor neurons 24 and 48 h after the conjoint stimulation of nerves P8 and P9. Thus changes in these biophysical properties do not appear to contribute to the expression of long-term facilitation. 5. The finding that conjoint stimulation of three nerves, P7, P8, and P9, produced no long-term facilitation raised the possibility that stimulation of nerve P7 alone might produce long-term inhibition that opposes the facilitatory effects induced by conjoint stimulation of nerves P8 and P9. Stimulation of nerve P7 alone, however, had no long-term inhibitory effect on the EPSPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗