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PubMed2000

Bilateral receptive field neurons and callosal connections in the somatosensory cortex.

Earlier studies recording single neuronal activity with bilateral receptive fields in the primary somatosensory cortex of monkeys and cats agreed that the bilateral receptive fields were related exclusively to the body midline and that the ipsilateral information reaches the cortex via callosal connections since they are dense in the cortical region representing the midline structures of the body while practically absent in the regions representing the distal extremities. We recently found a substantial number of neurons with bilateral receptive fields on hand digits, shoulders-arms or legs-feet in the caudalmost part (areas 2 and 5) of the postcentral gyrus in awake Japanese monkeys (Macaca fuscata). I review these results, discuss the functional implications of this bilateral representation in the postcentral somatosensory cortex from a behavioural standpoint and give a new interpretation to the midline fusion theory.

Animals↗
PubMed1998

A protein related to p21-activated kinase (PAK) that is involved in neurogenesis in the Drosophila adult central nervous system.

Brains are organized by the developmental processes generating them. The embryonic neurogenic phase of Drosophila melanogaster has been studied in detail at the genetic, cellular and molecular level. In contrast, much of what is known of postembryonic brain development has been gathered by neuroanatomical and gene expression studies. The molecular mechanisms underlying cellular diversity and structural organisation in the adult brain, such as the establishment of the correct neuroblast number, the spatial and temporal control of neuroblast proliferation, cell fate determination, and the generation of the precise pattern of neuronal connectivity, are largely unknown. In a screen for viable mutations affecting adult central brain structures, we isolated the mushroom bodies tiny (mbt) gene of Drosophila, which encodes a protein related to p21-activated kinase (PAK). We show that mutations in mbt primarily interfere with the generation or survival of the intrinsic cells (Kenyon cells) of the mushroom body, a paired neuropil structure in the adult brain involved in learning and memory.

Amino Acid Sequence↗
PubMed2005

Structural plasticity in the developing visual system.

The visual system has been used extensively to study cortical plasticity during development. Seminal experiments by Hubel and Wiesel (Wiesel, T.N. and Hubel, D.H. (1963) Single cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol., 26: 1003-1017.) identified the visual cortex as a very attractive model for studying structural and functional plasticity regulated by experience. It was discovered that the thalamic projections to the visual cortex, and neuronal connectivity in the visual cortex itself, were organized in alternating columns dominated by input from the left or the right eye. This organization was shown to be strongly influenced by manipulating binocular input during a specific time point of postnatal development known as the critical period. Two chapters in this volume review the molecular and functional aspects of this form of plasticity. This chapter reviews the structural changes that occur during ocular dominance (OD) plasticity and their possible functional relevance, and discusses developments in the methods that allow the analysis of the molecular and cellular mechanisms that regulate them.

Animals↗
PubMed1992

Descending projections from the subparafascicular thalamic nucleus to the lower brain stem in the rat.

In the course of our study on the neuronal connections of the subparafascicular nucleus (SPF) in the rat, descending projections from the SPF to the lower brain stem were examined by using the anterograde tracer PHA-L (Phaseolus vulgaris leukoagglutinin) and retrograde tracer WGA-HRP (horseradish peroxidase conjugated to wheat germ agglutinin). When PHA-L was injected into the magnocellular and/or parvicellular division of the SPF (SPFm and/or SPFp), presumed terminal labeling was seen, bilaterally with an ipsilateral dominance, in the mesencephalic and pontine central gray matter, peripheral shell regions of the inferior colliculus, cuneiform nucleus, and superior olivary complex (mainly in the superior paraolivary nucleus, and additionally in the nuclei of the trapezoid body). A few labeled axon terminals were also seen in the cochlear nuclei bilaterally with a contralateral dominance. In the second set of experiments, WGA-HRP was injected into the inferior colliculus, superior olivary complex, or cochlear nuclei. When WGA-HRP was injected into the peripheral shell regions of the inferior colliculus or the superior olivary complex, many labeled neuronal cell bodies were seen in the SPFm bilaterally with an ipsilateral dominance, and a moderate number of labeled neuronal cell bodies were observed in the SPFp (lateral SPF) bilaterally with an ipsilateral dominance. When WGA-HRP was injected into the cochlear nuclei, a moderate number of labeled neuronal cell bodies were observed in the SPFm and SPFp bilaterally with a contralateral dominance. The results indicate that the SPFm and SPFp (lateral SPF) of the rat send a considerable number of projection fibers to the lower brain stem. The target regions of these projection fibers include the auditory relay nuclei, such as the inferior colliculus, superior olivary complex, and cochlear nuclei.

Animals↗
PubMed2006

The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system.

During the development of the nervous system, outgrowing axons often have to travel long distances to reach their target neurons. In this process, outgrowing neurites tipped with motile growth cones rely on guidance cues present in their local environment. These cues are detected by specific receptors expressed on growth cones and neurites and influence the trajectory of the growing fibres. Neurite growth, guidance, target innervation and synapse formation and maturation are the processes that occur predominantly but not exclusively during embryonic or early post-natal development in vertebrates. As a result, a functional neural network is established, which is usually remarkably stable. However, the stability of the neural network in higher vertebrates comes at an expensive price, i.e. the loss of any significant ability to regenerate injured or damaged neuronal connections in their central nervous system (CNS). Most importantly, neurite growth inhibitors prevent any regenerative growth of injured nerve fibres. Some of these inhibitors are associated with CNS myelin, others are found at the lesion site and in the scar tissue. Traumatic injuries in brain and spinal cord of mammals induce upregulation of embryonic inhibitory or repulsive guidance cues and their receptors on the neurites. An example for embryonic repulsive directional cues re-expressed at lesion sites in both the rat and human CNS is provided with repulsive guidance molecules, a new family of directional guidance cues.

Animals↗
PubMed1997

Sacculocollic reflex arcs in cats.

Neuronal connections and pathways underlying sacculocollic reflexes were studied by intracellular recordings from neck extensor and flexor motoneurons in decerebrate cat. Bipolar electrodes were placed within the left saccular nerve, whereas other branches of the vestibular nerve were removed in the inner ear. To prevent spread of stimulus current to other branches of the vestibular nerve, the saccular nerve and the electrodes were covered with warm semisolid paraffin-Vaseline mixture. Saccular nerve stimulation evoked disynaptic (1.8-3.0 ms) excitatory postsynaptic potentials (EPSPs) in ipsilateral neck extensor motoneurons and di- or trisynaptic (1.8-4.0 ms) EPSPs in contralateral neck extensor motoneurons, and di- and trisynaptic (1.7-3.6 ms) inhibitory postsynaptic potentials (IPSPs) in ipsilateral neck flexor motoneurons and trisynaptic (2.7-4.0 ms) IPSPs in contralateral neck flexor motoneurons. Ipsilateral inputs were about twice as strong as contralateral ones to both extensor and flexor motoneurons. To determine the pathways mediating this connectivity, the lateral part of the spinal cord containing the ipsilateral lateral vestibulospinal tract (i-LVST) or the central part of the spinal cord containing the medial vestibulospinal tracts (MVSTs) and possibly reticulospinal fibers (RSTs) were transected at the caudal end of the C1 segment. Subsequent renewed intracellular recordings following sacculus nerve stimulation indicated that the pathway from the saccular nerve to the ipsilateral neck extensor motoneurons projects though the i-LVST, whereas the pathways to the contralateral neck extensors and to the bilateral neck flexor motoneurons descend in the MVSTs/RSTs. Our data show that sacculo-neck reflex connections display a qualitatively bilaterally symmetrical innervation pattern with excitatory connections to both neck extensor motoneuron pools, and inhibitory connections to both neck flexor motoneuron pools. This bilateral organization contrasts with the unilateral innervation scheme of the utriculus system. These results suggest a different symmetry plane along which sacculus postural reflexes are organized, thus supplementing the reference planes of the utriculus system and allowing the gravistatic system to represent all three translational spatial degrees of freedom. We furthermore suggest that the sacculocollic reflex plays an important role in maintaining the relative position of the head and the body against the vertical linear acceleration of gravity.

Afferent Pathways↗
PubMed2005

Light delays synaptic deafferentation and potentiates the survival of axotomized retinal ganglion cells.

Knowledge of the cellular mechanism underlying the therapeutic effect of stimulation and the optimal doses of such stimulation to maximize neuronal recovery is essential to guide clinical practice in neural rehabilitation. Using hamsters, we transected the optic nerve to demonstrate how light stimulation affects neuronal recovery. The c-fos protein was used as a neuronal connectivity marker. Here we show that: (a) in addition to cell death, a population of cells undergoes synaptic deafferentation and (b) light stimulation delays cell death and deafferentation. Among the three rearing conditions studied (6:18LD, 12:12LD, and 18:6LD), the 12:12LD condition appears to be the one achieving the optimal therapeutic effect. This study provides a solid base in the understanding of the neuroanatomical changes after traumatic brain injury and the need to establish an optimal level and timing for the environmental stimulation.

Animals↗
PubMed2004

Abnormalities of presynaptic protein CDCrel-1 in striatum of rats reared in social isolation: relevance to neural connectivity in schizophrenia.

Post-weaning social isolation-rearing of rats leads to behavioural and neurochemical sequelae that model aspects of schizophrenia, and it may be useful to test hypotheses related to putative molecular mechanisms of the illness. In humans, the presynaptic protein CDCrel-1 represents an interesting candidate molecule for the mechanism and aetiology of schizophrenia. CDCrel-1 modulates dopamine neurotransmission, binds to the SNARE protein syntaxin and maps onto a region of chromosome 22q11 deleted in velo-cardio-facial and DiGeorge syndromes, which are associated with increased prevalence of schizophrenia. Using the isolation-rearing model, we measured immunoreactivity of the synaptic proteins CDCrel-1, synaptophysin and syntaxin. Male, Sprague-Dawley rats were raised in groups or in isolation for 12 weeks from weaning. Synaptic protein immunoreactivities were measured in striatal and hippocampal homogenates, using a sensitive enzyme-linked immunoadsorbent assay with monoclonal antibodies. Isolation-rearing produced region- and protein-specific effects. CDCrel-1 immunoreactivity was significantly lower in the striatum and marginally higher in the hippocampus of isolation-reared compared with socially reared animals. There were no statistically significant differences in synaptophysin immunoreactivity in either region. Confocal microscopy demonstrated a high degree of colocalization between the two presynaptic proteins. In striatum, a robust relationship between CDCrel-1 and syntaxin immunoreactivities was observed in socially reared rats, this was lost in the isolation-reared animals. Altered levels of the septin CDCrel-1 in isolation-reared rats may contribute to changes in neuronal connectivity and neurotransmission, and suggest a potential role for CDCrel-1 in schizophrenia related to chromosome 22q11 deletion syndrome.

Animals↗
PubMed1968

Neuronal geometry: determination with a technique of intracellular dye injection.

In a study of the specificity of neuronal connections in lobster abdominal ganglia, the dye Procion Yellow M4RS was electrophoretically injected into identified cell bodies. This dye spreads into fine branches of cells, survives fixation and routine histological procedures, and permits the reconstruction of cell shapes through examination of serial sections of ganglia. Certain cells were found to have an internal bilateral symmetry. Repeated injection of the same cells in ganglia from different animals showed that cells have characteristic shapes and that the neuropil is highly structured. This method of dye injection should have general applicability in studies where a knowledge of the geometry of specific cells is important.

Animals↗
PubMed2004

Clinical disorders of brain plasticity.

Clinical disorders of brain plasticity are common in the practice of child neurology. Children have an enhanced capacity for brain plasticity compared to adults as demonstrated by their superior ability to learn a second language or their capacity to recover from brain injuries or radical surgery such as hemispherectomy for epilepsy. Basic mechanisms that support plasticity during development include persistence of neurogenesis in some parts of the brain, elimination of neurons through apoptosis or programmed cell death, postnatal proliferation and pruning of synapses, and activity-dependent refinement of neuronal connections. Brain plasticity in children can be divided into four types: adaptive plasticity that enhances skill development or recovery from brain injury; impaired plasticity associated with cognitive impairment; excessive plasticity leading to maladaptive brain circuits; and plasticity that becomes the brain's 'Achilles' Heel' because makes it vulnerable to injury. A broad group of pediatric neurologic disorders can be understood in terms of their impact on fundamental mechanisms for brain plasticity. These include neurofibromatosis, tuberous sclerosis, Fragile X syndrome, other inherited forms of mental retardation, cretinism, Coffin-Lowry syndrome, lead poisoning, Rett syndrome, epilepsy, hypoxic-ischemic encephalopathy and cerebral palsy.

Animals↗
PubMed2003

Brain plasticity in paediatric neurology.

Plasticity includes the brain's capacity to be shaped or moulded by experience, the capacity to learn and remember, and the ability to reorganize and recover after injury. Mechanisms for plasticity include activity-dependent refinement of neuronal connections and synaptic plasticity as a substrate for learning and memory. The molecular mechanisms for these processes utilize signalling cascades that relay messages from synaptic receptors to the nucleus and the cytoskeleton to control the structure of axons and dendrites. Several paediatric neurological disorders such as neurofibromatosis-1, Fragile X syndrome, Rett syndrome, and other syndromic and non-specific forms of mental retardation involve lesions in these signalling pathways. Acquired disorders such as hypoxic-ischaemic encephalopathy, lead poisoning and epilepsy also involve signalling pathways including excitatory glutamate receptors. Information about these 'plasticity pathways' is useful for understanding their pathophysiology and potential therapy.

Adaptation, Physiological↗
PubMed1999

Tone burst-evoked myogenic potentials in human neck flexor and extensor.

Vestibular evoked myogenic potential (VEMP) has been proposed to be a manifestation of sacculocollic reflex. In a recent study using intracellular recording from neck flexor and extensor motoneurons, the neuronal connections and pathways underlying sacculocollic reflexes were determined in cats. The results showed that sacculocollic reflex displayed inhibitory connection to bilateral neck flexors and excitatory connection to bilateral neck extensors. A total of 16 normal young adults were tested with bilateral recordings of sternocleidomastoid (SCM) and splenius capitis (SC) muscles by acoustic stimulus of 500 Hz short tone burst. The results revealed that polarity of the wave I/II of VEMP on SC was the reverse of that on SCM. This implied that VEMP from ipsilateral SCM showed inhibitory neural activity; whereas VEMP from ipsilateral SC was an excitatory response. Using this non-invasive technique, the sacculocollic reflexes in human neck flexor and extensor were studied. The results in humans were consistent with the previous findings in cats.

Acoustic Stimulation↗
PubMed2005

Slow endogenous activity transients and developmental expression of K+-Cl- cotransporter 2 in the immature human cortex.

Spontaneous transients of correlated activity are a characteristic feature of immature brain structures, where they are thought to be crucial for the establishment of precise neuronal connectivity. Studies on experimental animals have shown that this kind of early activity in cortical structures is composed of long-lasting, intermittent network events, which undergo a developmental decline that is closely paralleled by the maturation of GABAergic inhibition. In order to examine whether similar events occur in the immature human cortex, we performed direct current-coupled electroencephalography (EEG) recordings from sleeping preterm babies. We show now that much of the preterm EEG activity is confined to spontaneous, slow activity transients. These transients are characterized by a large voltage deflection that nests prominent oscillatory activity in several frequency bands covering the whole frequency spectrum of the preterm EEG (<0.1-30 Hz). The slow voltage deflections had an amplitude of up to 800 microV. Most of these 'giant' events originated in the temporo-occipital areas, with a maximum rate of about 8/min, and their occurrence as well as amplitude showed a decline by the time of normal birth. In age-matched fetal brain tissue, this decrease in the spontaneous activity transients was associated with a developmental up-regulation of the neuronal chloride extruder K+-Cl- cotransporter 2, a crucial molecule for the generation of inhibitory GABAergic Cl- currents. Our work indicates that slow endogenous activity transients in the immature human neocortex are mostly confined to the prenatal stage and appear to be terminated in parallel with the maturation of functional GABAergic inhibition.

Cerebral Cortex↗
PubMed2001

Role of AMPA receptor endocytosis in synaptic plasticity.

Activity-mediated changes in the strength of synaptic communication are important for the establishment of proper neuronal connections during development and for the experience-dependent modification of neural circuitry that is believed to underlie all forms of behavioural plasticity. Owing to the wide-ranging significance of synaptic plasticity, considerable efforts have been made to identify the mechanisms by which synaptic changes are triggered and expressed. New evidence indicates that one important expression mechanism of several long-lasting forms of synaptic plasticity might involve the physical transport of AMPA-type glutamate receptors in and out of the synaptic membrane. Here, we focus on the rapidly accumulating evidence that AMPA receptors undergo regulated endocytosis, which is important for long-term depression.

Animals↗
PubMed2004

The concept of 'developing the brain': a new natural science for learning and education.

From the viewpoint of biology, learning and education can be defined as the processes of forming neuronal connections in response to external environmental stimuli, and of controlling or adding appropriate stimuli, respectively. Learning and education can thus be studied as a new field of natural sciences with the entire human life span as its subject, thus including various problems such as fetal environment, childcare, language acquisition, general/special education, and rehabilitation. Non-invasive imaging of higher-order brain functions in humans will clarify the brain's developmental processes, and will provide various evidence for learning sciences. This new approach is called 'developing the brain' or 'brain science and education'. The origin of the concept and its present state are described and its future prospects are briefly analyzed.

Brain↗
PubMed2002

NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity.

Dynamic regulation of synaptic efficacy is thought to play a crucial role in formation of neuronal connections and in experience-dependent modification of neural circuitry. The molecular and cellular mechanisms by which synaptic changes are triggered and expressed are the focus of intense interest. This articles reviews recent evidence that NMDA receptors undergo dynamically regulated targeting and trafficking, and that the physical transport of NMDA receptors in and out of the synaptic membrane contributes to several forms of long-lasting synaptic plasticity. The identification of targeting and internalization sequences in NMDA-receptor subunits has begun the unraveling of some mechanisms that underlie activity-dependent redistribution of NMDA receptors. Given that NMDA receptors are widely expressed throughout the CNS, regulation of NMDA-receptor trafficking provides a potentially important way to modulate efficacy of synaptic transmission.

Animals↗
PubMed1999

Cholinergic and GABAergic neuronal elements in the pineal organ of lampreys, and tract-tracing observations of differential connections of pinealofugal neurons.

The putative cholinergic and GABAergic elements of the pineal organ of lampreys were investigated with immunocytochemistry to choline acetyltransferase (ChAT) and gamma-aminobutyric acid (GABA), and by acetylcholinesterase (AChE) histochemistry. For comparison we also carried out immunocytochemistry to serotonin (5-HT) and a tract-tracing investigation of the two types of projecting cells, i. e., ganglion cells and long-axon photoreceptors. Most photoreceptors were ChAT-immunoreactive (ChAT-ir) and AChE-positive, while ganglion cells and the pineal tract were ChAT-negative and AChE-negative or only faintly positive. These results strongly suggest the presence of a cholinergic system of photoreceptors in the lamprey pineal organ. GABA-ir fibers that appear to originate from faintly to moderately stained ganglion cells were observed in the pineal stalk. Immunocytochemistry to 5-HT indicated the presence of two types of 5-HT-ir cells, bipolar cells and ganglion-like cells. The connections of the ganglion cells and long-axon photoreceptors were also studied by application of DiI to the pineal stalk in fixed brains or of biotinylated dextran amine (BDA) to one of the main targets of pinealofugal fibers (optic tectum or mesencephalic tegmentum) in isolated brains in vitro. Some long-axon photoreceptors and ganglion cells were labeled from the optic tectum. However, BDA application to the tegmentum exclusively labeled ganglion cells in the pineal organ. These results indicate that the two morphological types of afferent pineal neuron have different projections. No labeled cells were observed in the parapineal organ in BDA experiments, indicating that this organ and the pineal organ are involved in different neural circuits.

Animals↗
PubMed1996

Late development of Zif268 ocular dominance columns in primary visual cortex of primates.

Zif268 transcription factor is expressed throughout Cebus apella visual cortex at high basal levels. Monocular eyelid suture alters the levels of Zif268 on neurons connected to the deprived eye, revealing ocular dominance columns in the striate cortex of Cebus as previously demonstrated in Old World monkeys (Chaudhuri and Cynader, Brain Res., 605 (1993) 349-353). Zif268 ocular dominance columns are revealed in adult Cebus monkey after 24-48 h of monocular deprivation, but not in infant monkeys up to 3 months of age. In 6-month-old Cebus monkeys, Zif268 ocular dominance columns are still poorly defined. These results suggest that Zif268 ocular dominance columns establish late during normal primate visual system development, and that some degree of visual plasticity is still present at this age in the Cebus monkey.

Aging↗