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At least 253 records · Page 14Linked to original sources
PubMed2002

Spine motility. Phenomenology, mechanisms, and function.

Throughout the history of neuroscience, dendritic spines have been considered stable structures, but in recent years, imaging techniques have revealed that spines are constantly changing shape. Spine motility is difficult to categorize, has different forms, and possibly even represents multiple phenomena. It is influenced by synaptic transmission, intracellular calcium, and a multitude of ions and other molecules. An actin-based cascade mediates this phenomenon, and while the precise signaling pathways are still unclear, the Rho family of GTPases could well be a "common denominator" controlling spine morphology. One role of spine motility might be to enable a searching function during synaptogenesis, allowing for more efficacious neuronal connectivity in the neuronal thicket. This idea revisits concepts originally formulated by Cajal, who proposed over a hundred years ago that spines might help to increase and modify synaptic connections.

Animals↗
PubMed1993

Activity-dependent refinement of inhibitory connections.

Several lines of evidence suggest that excitatory synaptic transmission contributes to the maturation of precise neuronal connections. In the present study we determined whether the specific innervation pattern of single inhibitory arborizations was dependent upon neuronal activity during development. A homogeneous group of glycinergic inhibitory neurons in the central auditory system, the medial nucleus of the trapezoid body (MNTB), was functionally denervated in neonatal gerbils. The anatomical specificity of single MNTB terminal arborizations was subsequently measured along the tonotopic axis of a postsynaptic target, the lateral superior olive. Here we demonstrate that inhibitory terminal boutons spread a significantly greater distance along the frequency axis of the postsynaptic target following functional denervation. Although total arbor length remained unchanged, there was a significant increase in the number of branch points, suggesting de novo sprouting. The results indicate that normal inhibitory synaptic activity contributes to the developmental refinement of specific neuronal connections.

Acoustic Stimulation↗
PubMed2001

Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia.

Schizophrenia has been associated with anatomical and functional abnormalities of the dorsolateral prefrontal cortex (DLPFC), which may reflect abnormal connections of DLPFC neurons. We measured mRNA levels of growth-associated protein (GAP-43), a peptide linked to the modifiability of neuronal connections, in post-mortem brain tissue from two cohorts of patients with schizophrenia and controls. Using the RNase protection assay (RPA), we found a significant reduction in GAP-43 mRNA in the DLPFC, but not in the hippocampus, of patients with schizophrenia. With in situ hybridization histo- chemistry (ISHH), performed on a separate cohort, we confirmed the reduction of GAP-43 mRNA in the DLPFC of patients with schizophrenia. We detected reduced GAP-43 mRNA per neuron in layers III, V and VI of patients with schizophrenia compared with normal controls and patients with bipolar disorder. Thus, glutamate neurons in DLPFC of schizophrenic patients may synthesize less GAP-43, which could reflect fewer and/or less modifiable connections than those in normal human brain, and which may be consistent with the deficits of prefrontal cortical function that characterize schizophrenia.

Adult↗
PubMed2004

Longterm stability and developmental changes in spontaneous network burst firing patterns in dissociated rat cerebral cortex cell cultures on multielectrode arrays.

Spontaneous action potentials were recorded longitudinally for 4-7 weeks from dissociated rat occipital cortex cells cultured on planar multi-electrode plates, during their development from isolated neurons into synaptically connected neuronal networks. Activity typically consisted of generalized bursts lasting up to several seconds, separated by variable epochs of sporadic firing at some of the active sites. These network bursts displayed discharge patterns with age-dependent firing rate profiles, and durations significantly increasing in the 3rd week in vitro and decreasing after about 1 month in vitro, when they evolved into short events with prompt onsets. These findings indicate that after about a month in vitro these cultured neuronal networks have developed a degree of excitability that allows almost instantaneous triggering of generalized discharges. Individual neurons tend to fire in specific and persistent temporal relationships to one another within these network bursts, suggesting that network connectivity maintains a core topology during its development.

Action Potentials↗
PubMed1984

A quantitative analysis of the spatial organization of the vestibulo-ocular reflexes in lateral- and frontal-eyed animals--II. Neuronal networks underlying vestibulo-oculomotor coordination.

The neuronal connectivity underlying the vestibulo-ocular reflexes in cat and rabbit was evaluated in the light of quantitative data of the spatial orientation on semicircular canals and extraocular muscles. Neuronal connectivity was calculated using a matrix-analysis of the sensory and motor periphery, and of the brain stem pathways connecting semicircular canals and extraocular muscles. Two cases of vestibulo-ocular reflex compensation were considered. In the first case, vestibulo-oculor reflex compensation was assumed to be isotropic, i.e. the vestibulo-ocular reflex gain is the same for all directions of rotation. In the second case, the vestibulo-oculor reflex gain was assumed to be anisotropic with the "torsional" gain smaller than the "horizontal" and "vertical" gains. The theoretical calculation predicts that besides the principal vestibulo-ocular reflex pathways (classical three-neuron-arc connectivity), several accessory connections (other than principal connections, regardless of the synapses involved) exist which are characteristic for each species. These accessory connections were compared to physiological and anatomical data. In the cat theoretical connections for an isotropic vestibulo-ocular reflex gain agree with pathways observed experimentally, of which the most characteristic are excitatory connections to the superior rectus and inhibitory connections to the inferior rectus muscle from both of the anterior canals, and a mirror image pattern of connections from the posterior canals. In the rabbit experimentally obtained data and calculated connections rarely agree. However, for an anisotropic gain we find a higher rate of coincidence between experimental and theoretical connections. Our evaluation indicates, that accessory vestibulo-ocular reflex pathways serve to compensate for the incongruence between semicircular canal and extraocular muscle planes, at least in the cat. Available experimental data suggest an important role of a special subclass of accessory pathways via axon collaterals of principal projections (three-neuron-arc nature). With certain restrictions, the presented method of calculation promises to be a useful tool for a quantitative analysis of the vestibulo-ocular reflex.

Animals↗
PubMed2000

[The brain is shaped by stimulation and challenge].

The healthy adult brain retains a certain capacity for plasticity and functional reorganization throughout the life span. Morphologic, neuropsychological and neuroimaging studies have demonstrated that neuronal connections and cortical maps can be remodeled by our experience and activities. Activity-induced increase in neuronal connections may to some extent compensate for neuronal loss during aging. Increased knowledge of the potential capability of the adult brain to compensate for brain lesions is likely to improve rehabilitation strategies.

Adult↗
PubMed1978

Intracortical horizontal connections of neurons in cat and monkey motor cortex.

The present paper deals with the study of the structure of horizontal neuron chains, one of the aspects of intracortical intraneuronal relationships. The motor cortex (field 4) of cats and lower monkeys (Papio hamadryas and Macacus rhesus s. M. mullata) was treated by the impregnating method of Golgi--Kopsh. The drawings of neurons from 90-micrometer sections were made by means of a camera lucida. Three possible pathways of impulse transmission along neuron chains in a horizontal direction were revealed. These were: a pyramido-pyramidal system of connections which may possibly spread excitatory influence among several columns; a basket-pyramidal connection system; and connections which arise from successive switchings between neighboring neurons of one layer.

Animals↗
PubMed1990

Synaptic connections of neurones identified by Golgi impregnation: characterization by immunocytochemical, enzyme histochemical, and degeneration methods.

For more than a century the Golgi method has been providing structural information about the organization of neuronal networks. Recent developments allow the extension of the method to the electron microscopic analysis of the afferent and efferent synaptic connections of identified, Golgi-impregnated neurones. The introduction of degeneration, autoradiographic, enzyme histochemical, and immunocytochemical methods for the characterization of Golgi-impregnated neurones and their pre- and postsynaptic partners makes it possible to establish the origin and also the chemical composition of pre- and postsynaptic elements. Furthermore, for a direct correlation of structure and function the synaptic interconnections between physiologically characterized, intracellularly HRP-filled neurones and Golgi-impregnated cells can be studied. It is thought that most of the neuronal communication takes place at the synaptic junction. In the enterprise of unravelling the circuits underlying the synaptic interactions, the Golgi technique continues to be a powerful tool of analysis.

Animals↗
PubMed1995

The acoustic startle reflex: neurons and connections.

The startle reflex protects animals from blows or predatory attacks by quickly stiffening the limbs, body wall and dorsal neck in the brief time period before directed evasive or defensive action can be performed. The acoustic startle reflex in rats and cats is mediated primarily by a small cluster of giant neurons in the ventrocaudal part of the nucleus reticularis pontis caudalis (RPC) of the reticular formation. Activation of these RPC neurons occurs 3-8 ms after the acoustic stimulus reaches the ear. Undetermined neurons of the cochlear nuclei activate RPC via weak monosynaptic and strong disynaptic connections. The strong disynaptic input occurs via neurons of the contralateral ventrolateral pons, including large neurons of the ventrolateral tegmental nucleus that integrate auditory, tactile and vestibular information. RPC giant neurons, in turn, activate hundreds of motoneurons in the brain stem and the length of the spinal cord via large reticulospinal axons near the medial longitudinal fasciculus. To hindlimb motoneurons, monosynaptic connections from the reticulospinal tract are weak, but disynaptic connections via spinal cord interneurons are stronger and show temporal facilitation, like the startle response itself.

Animals↗
PubMed1991

Monosynaptic connections between neurons of trigeminal mesencephalic nucleus and jaw-closing motoneurons in the rat: an intracellular horseradish peroxidase labelling study.

In order to confirm the monosynaptic connections of muscle spindle-mediated jaw stretch reflexes, 8 neurons of trigeminal mesencephalic nucleus innervating masseteric muscle spindles were identified electrophysiologically and stained intracellularly with horseradish peroxidase. These axon terminals projected to ipsilateral dorsal and dorsolateral divisions of trigeminal motor nucleus and extensive premotor areas. Under electron microscope, labeled terminals made monosynaptic contacts predominantly with dendrites in the jaw-closing motoneuron pools. One labeled and many non-labeled terminals were frequently observed to converge simultaneously on one dendrite in the area. However, it was of particular interest that 28% of the labeled terminals constituted the intermediate component of axo-axodendritic synaptic triads. The present study confirmed, for the first time, monosynaptic connections between jaw-closing muscle spindle afferents and jaw-closing motoneurons. These findings also provided ultrastructural evidence for the monosynaptic excitation of muscle spindle-mediated jaw stretch reflexes which received presynaptic and postsynaptic inhibitions of the premotor neurons from other sources.

Animals↗
PubMed1996

[Neural pathways--neural networks].

During the past two decades, the introduction of several modern neuroanatomical approaches resulted in a rapidly growing body of informations about neuronal pathways in the central nervous system. Several new neuronal connections between brain areas have been discovered, and the chemical nature (neurotransmitter content) of pathways has been determined by using highly specific neurochemical and immunohistochemical techniques. On the basis of these new informations, our knowledge and attitude to the general organization of neuronal connections have been changed substantially: 1. Neuronal pathways are multi-neuronal networks rather than simple chain of neurons, wherein informations are forwarded between two brain areas bidirectionally, meanwhile several additional brain regions are inter-connected by axon-collaterals. 2. A single neuronal cell may synthesize several neuropeptides which co-localized in and released from nerve terminals, and depending on the target sites they may act as neurotransmitters or neurohormones. In certain conditions, neuropeptides may also function as nerve growth factors by supporting the survival or the restitution of neuronal cells. 3. By the introduction of molecular imaging in neuroscience (visualization of oncogenes, specific mRNA's, etc), topographical studies on neuronal pathways are more and more completed by functional informations.

Brain↗
PubMed1986

Development of anomalous retinal projections to nonvisual thalamic nuclei in Syrian hamsters: a quantitative study.

When two of the principal targets of retinofugal axons, the superior colliculus and dorsal nucleus of the lateral geniculate body, are ablated in newborn hamsters and the somatosensory (ventrobasal) or auditory (medial geniculate) thalamic nuclei are partially deafferented, the optic axons form permanent, abnormal connections in the latter nuclei. The lateral posterior nucleus of the operated hamsters also receives an anomalously large retinal projection. Here, we report on the results of a quantitative study that was undertaken in order to elucidate how these abnormal connections are formed. In normal, newborn hamsters, there is a transient retinal projection to the ventrobasal nucleus that disappears 3-4 days postnatally. Our quantitative data show that postoperatively, the volume of the retino-ventrobasal projection increases proportionately more than the volume of the ventrobasal nucleus so that the retino-ventrobasal projection in operated adult hamsters is due both to the stabilization of the normally transient projection and to a reactive sprouting that increases the size of the projection. The retino-medial geniculate projection arises de novo by reactive sprouting of optic tract fibers that normally pass over and through the nucleus; in unoperated hamsters, terminating projections are never seen at any age. The quantitative data also show that the anomalously large retino-lateral posterior projection is due almost entirely to the reactive sprouting of the normal projection and/or normal fibers of passage that are already present on the day of birth, although it is possible that a minor component can be attributed to the stabilization of a small population of normally transient retino-lateral posterior axons. The present results demonstrate that the transient retino-ventrobasal axons in normal, newborn hamsters are capable of making permanent connections with ventrobasal neurons. This finding raises the important question of the cellular mechanisms that determine whether immature neuronal connections are stabilized or eliminated. The results also suggest that during both normal and abnormal development, the choice of a target by growing axons may depend upon the axons being in proximity to a potential terminal site just at the time when that site is capable of receiving afferents.

Animals↗
PubMed1993

Reference of pain following percutaneous cervical cordotomy.

In order to clarify the mechanism of reference of pain following cordotomy (ROPC), the authors investigated ROPC in 66 patients undergoing percutaneous cervical cordotomy (PCC) and examined the features of ROPC and the correlation between the occurrence of ROPC and the pre-operative pain states, as well as the results of PCC. ROPC was observed in 7 patients. It occurred immediately after PCC in 6 of 7 patients and 6 h after PCC in 1 patient. The pain was referred horizontally and cranially from the region rendered totally or largely analgesic by PCC to the normally innervated region. The region to which the pain was referred was not fixed. The referred pain disappeared by rendering the region where referred pain was felt analgesic with additional PCC. There was no correlation between the occurrence of ROPC and pre-operative pain states, or the results of PCC. From these results we postulate that: (1) ROPC occurs via a subsidiary pathway consisting of ascending chains of short neurons connecting dorsal horn neurons longitudinally and latitudinally; (2) the subsidiary pathway is inhibited under normal conditions by feedback inhibition from second-order neurons and/or higher central neurons of the nociceptive pathway; and (3) ROPC results from the release of the feedback inhibition by cordotomy.

Adolescent↗
PubMed2001

Metabolically active rat brain slices as a model to study the regulation of protein phosphorylation in mammalian brain.

The reversible protein phosphorylation is the most important cellular regulation of the biological functions of many proteins. Disregulation of protein phosphorylation is involved in pathogeneses of several human diseases. The abnormal hyperphosphorylation of microtubule-associated protein tau and its aggregation into neurofibrillary tangles in selective neurons is one of the major brain pathologies of Alzheimer's disease and several other related neurodegenerative diseases. Here we present metabolically competent rat brain slices as a model to study the regulation of protein phosphorylation in brain. Employing this model we have been able to study the abnormal hyperphosphorylation of tau and other microtubule-associated proteins. We have evaluated the activity and intactness of the rat brain slices both biochemically and morphologically. Selective inhibition of protein phosphatase 2A in these rat brain slices by the treatment with okadaic acid induced hyperphosphorylation of tau at many abnormal sites seen in Alzheimer's disease brain and the accumulation of hyperphosphorylated tau in pyramidal neurons of the cortex and hippocampus. The regulation of the phosphorylation of high-molecular-weight microtubule-associated protein, MAP1b, was also studied with this model. This model enables studies on the regulation of protein phosphorylation not only biochemically, but also histochemically and immunocytochemically. Furthermore, unlike cultured cells, the neurons in the brain slices reside in the physiological environment of the brain consisting of natural extracellular matrix, neuronal connectivity, and neuronal-glial interactions.

Alzheimer Disease↗
PubMed1995

Glutamate-evoked release of adenosine 5'-triphosphate causing an increase in intracellular calcium in hippocampal neurons.

ATP evoked an increase in intracellular Ca2+ concentration ([Ca]i) in hippocampal neurons in the presence of tetrodotoxin (TTX, 3 microM), hexamethonium (C6, 100 microM), D-2-amino-phosphonovalerate (APV, 100 microM), 6-cyano-7-nitro quinoxalline-2,3-dione (CNQX, 30 microM), bicuculline (10 microM) and cadmium (Cd2+, 300 microM). The increase was blocked by suramin (100 microM), a P2-purinoceptor blocker. These results suggest that ATP evokes an increase in [Ca]i through P2-purinoceptor. As a result of measuring [Ca]i in multiple cells simultaneously, it was suggested that glutamatergic neurones connect with purinergic neurones and glutamate (10 microM) stimulated the release of ATP causing an increase in [Ca]i in postsynaptic neurones.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

Neuronal death induced by endogenous extracellular ATP in retinal cholinergic neuron density control.

The precise assembly of neuronal circuits requires that the correct number of pre- and postsynaptic neurons form synaptic connections. Neuronal cell number is thus tightly controlled by cell death during development. Investigating the regulation of cell number in the retina we found an ATP gated mechanism of neuronal death control. By degrading endogenous extracellular ATP or blocking the P2X(7) ATP receptors we found that endogenous extracellular ATP triggers the death of retinal cholinergic neurons during normal development. ATP-induced death eliminates cholinergic cells too close to one another, thereby controlling the total number, the local density and the regular spacing of these neurons.

Adenosine Triphosphate↗