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PubMed1984

Focal cortical seizures prevent HRP and HRP-WGA labeling only in neurons bidirectionally connected to the cortex.

Intracortical implants of polyacrylamide gel containing horseradish peroxidase labeled cortical efferents and perikarya in some cortical areas and a number of subcortical formations. When epileptogenic penicillin was added to the gel, no labeling was seen in the efferents and cell bodies of the cortex, thalamus, or claustrum, whereas the magnocellular nuclei of the basal forebrain, raphe nuclei and locus coeruleus did contain the label.

Animals↗
PubMed2006

Tinnitus sensitization: Sensory and psychophysiological aspects of a new pathway of acquired centralization of chronic tinnitus.

OBJECTIVE: Acquired centralized tinnitus (ACT) is the most frequent form of chronic tinnitus. The proposed ACT sensitization (ACTS) assumes a peripheral initiation of tinnitus whereby sensitizing signals from the auditory system establish new neuronal connections in the brain. Consequently, permanent neurophysiological malfunction within the information-processing modules results. Successful treatment has to target these malfunctioning information processing. We present in this study the neurophysiological and psychophysiological aspects of a recently suggested neurophysiological model, which may explain the symptoms caused by central cognitive tinnitus sensitization. Although conditioned reflexes, as a causal agent of chronic tinnitus, respond to extinction procedures, sensitization may initiate a vicious circle of overexcitation of the auditory system, resisting extinction and habituation. DATA SOURCES: We used the literature database as indicated under "References" covering English and German works. STUDY SELECTION: For the ACTS model we extracted neurophysiological hypotheses of the auditory stimulus processing and the neuronal connections of the central auditory system with other brain regions to explain the malfunctions of auditory information processing. The model does not assume information-processing changes specific for tinnitus but treats the processing of tinnitus signals comparable with the processing of other external stimuli. The model uses the extensive knowledge available on sensitization of perception and memory processes and highlights the similarities of tinnitus with central neuropathic pain. DATA EXTRACTION: Quality, validity, and comparability of the extracted data were evaluated by peer reviewing. DATA SYNTHESIS: Statistical techniques were not used. CONCLUSION: According to the tinnitus sensitization model, a tinnitus signal originates (as a type I-IV tinnitus) in the cochlea. In the brain, concerned with perception and cognition, the 1) conditioned associations, as postulated by the tinnitus model of Jastreboff, and the 2) unconditioned sensitized stimulus responses, as postulated in the present ACTS model, are actively connected with and attributed to the tinnitus signal. Attention to the tinnitus constitutes a typical undesired sensitized response. Some of the tinnitus-associated attributes may be called essential, unconditioned sensitization attributes. By a process called facilitation, the tinnitus' essential attributes are suggested to activate the tinnitus response. The result is an undesired increase in responsivity, such as an increase in attentional focus to the eliciting tinnitus stimulus. The mechanisms underlying sensitization are known as a specific nonassociative learning process producing a structural fixation of long-term facilitation at the synaptic level. This sensitization model may be important for the development of a sensitization-specific treatment if extinction procedures alone do not lead to satisfactory outcome. Inasmuch as this model considers sensitization as a nonassociative learning process based on cortical plasticity, it is reasonable to assume that this learning process can be altered by counteracting learning procedures. These counteracting learning procedures may consist of tinnitus-specific cognitive and behavioral procedures.

Adaptation, Psychological↗
PubMedDate not supplied

[The monosynaptic connection between identified neurons in the snail].

Monosynaptic connection between two identified neurones was investigated using electrophysiological and morphological methods in preparation of isolated nervous system of the snail Achatina fulica. Intracellular pressure injection of cobalt chloride was used for staining of neuronal branches. Electrophysiologically revealed synaptic connection between two giant neurones was identified to be monosynaptic by morphological methods.

Animals↗
PubMed2000

Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage.

The role of focal brain damage as a trigger for autoimmune inflammation in multiple sclerosis (MS) is unclear. In this study we examine mechanisms by which experimental autoimmune encephalomyelitis (EAE) is enhanced by focal brain damage. EAE was produced in Lewis rats by footpad inoculation; focal brain damage, in the form of a cortical cryolesion (cryolesion-EAE), was induced 8 days post-inoculation (d.p.i.). The distribution of inflammation and chemokine production in cryolesion-EAE and EAE-only were compared. Inflammation in the brain, measured by immunocytochemistry for T lymphocytes (W3/13) and microglial activation (MHC class II -OX6), was significantly enhanced in cryolesion-EAE 11-15 d.p.i. (p < 0.01-0.05) but by 20-40 d.p.i., equated with EAE-only. Inflammation in cryolesion-EAE related to breakdown of the blood-brain barrier (BBB) at the site of the cryolesion and also to the corticospinal tracts and thalamus, reflecting the afferent and efferent neuronal connections with the cryolesioned cortex. Semiquantitative RT/PCR dot-blot hybridization assay showed a 6-fold increase in mRNA for specific chemokines in the brain in cryolesion-EAE at 9 d.p.i. (MCP-1) and 11 d.p.i. (MCP-1 and MCP-5) with no significant increase in RANTES, GRO-alpha, or MIP-1alpha. By 14 d.p.i., the levels of MCP-1 and MCP-5 mRNA equated with EAE-only animals. These results suggest that enhancement and location of autoimmune inflammation in the brain following focal cortical injury initially involve chemokines such as the macrophage chemoattractants MCP-1 and MCP-5, and the activities of afferent and efferent neuronal connections with the site of damage. By analogy, similar factors may modulate or reactivate autoimmune inflammation in MS.

Animals↗
PubMed2004

Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding.

Dscam is an immunoglobulin (Ig) superfamily protein required for the formation of neuronal connections in Drosophila. Through alternative splicing, Dscam potentially gives rise to 19,008 different extracellular domains linked to one of two alternative transmembrane segments, resulting in 38,016 isoforms. All isoforms share the same domain structure but contain variable amino acid sequences within three Ig domains in the extracellular region. We demonstrate that different isoforms exhibit different binding specificity. Each isoform binds to itself but does not bind or binds poorly to other isoforms. The amino acid sequences of all three variable Ig domains determine binding specificity. Even closely related isoforms sharing nearly identical amino acid sequences exhibit isoform-specific binding. We propose that this preferential homophilic binding specificity regulates interactions between cells and contributes to the formation of complex patterns of neuronal connections.

Alternative Splicing↗
PubMed2005

Comparative genomics and diversifying selection of the clustered vertebrate protocadherin genes.

To explain the mechanism for specifying diverse neuronal connections in the brain, Sperry proposed that individual cells carry chemoaffinity tags on their surfaces. The enormous complexity of these connections requires a tremendous diversity of cell-surface proteins. A large number of neural transmembrane protocadherin (Pcdh) proteins is encoded by three closely linked human and mouse gene clusters (alpha, beta, and gamma). To gain insight into Pcdh evolution, I performed comprehensive comparative cDNA and genomic DNA analyses for the three clusters in the chimpanzee, rat, and zebrafish genomes. I found that there are species-specific duplications in vertebrate Pcdh genes and that additional diversity is generated through alternative splicing within the zebrafish "variable" and "constant" regions. Moreover, different codons (sites) in the mammalian Pcdh ectodomains (ECs) are under diversifying selection, with some under diversity-enhancing positive Darwinian selection and others, including calcium-binding sites, under strong purifying selection. Interestingly, almost all positively selected codon positions are located on the surface of ECs 2 and 3. These diversified residues likely play an important role in combinatorial interactions of Pcdh proteins, which could provide the staggering diversity required for neuronal connections in the brain. These results also suggest that adaptive selection is an additional evolutionary factor for increasing Pcdh diversity.

Alternative Splicing↗
PubMed1995

Morphology and connections of neurons in area 17 projecting to the extrastriate areas MT and 19DM and to the superior colliculus in the monkey Callithrix jacchus.

Neurons of area 17, the primary visual cortex, project to various anatomically and physiologically different extrastriate areas and subcortical regions. In the present investigation, we addressed the question of whether the efferent neurons in area 17 can contribute to functional diversity between these regions. We approached this question by analyzing the dendritic morphology of neurons in area 17 projecting to area MT, area 19DM, and the superior colliculus in the new world simian primate Callithrix jacchus, because dendritic morphology is an important factor in determining physiological properties of nerve cells. Retrograde transport of fluorochromes injected into the target regions, and intracellular injections of Lucifer yellow in the prelabelled neurons, revealed the following. 1) Morphologically identical large pyramidal cells in layer VI of area 17 project to all three targets. Some of them possess axon collaterals to two or all three targets, suggesting that they provide common information to all three areas. 2) Pyramidal cells in layer IIIc projecting to area MT form a morphologically homogeneous population. 3) Three small to medium-sized pyramidal cell types in layers IIIa-c, spiny stellate cells in layer IIIc, and another large pyramidal cell type in layer VI project to area 19DM. 4) Pyramidal cells in the lower two-thirds of layer V in area 17 project to the superior colliculus. In conclusion, we have shown that in Callithrix one efferent pathway may originate from several cell types. However, with the exception of the large cells in layer VI, efferent cells projecting to area MT, area 19DM, and the superior colliculus were morphologically distinct. This suggests that functional differences between brain regions could arise in part from morphological heterogeneity between and within the efferent cell populations.

Animals↗
PubMed1994

Sex differences in the distribution and projections of testosterone target neurons in the medial preoptic area and the bed nucleus of the stria terminalis of rats.

Retrograde tracing was combined with steroid hormone autoradiography to investigate the projections of testosterone-target neurons in preoptic and limbic regions to the midbrain in male and female rats. Autoradiograms were prepared from the brains of male and female rats that had received an injection of a fluorescent retrograde tracer into the midbrain, and an intravenous injection of [3H]testosterone. Testosterone target neurons that project to the midbrain were abundant in the medial preoptic nucleus (MPN) and bed nucleus of the stria terminalis (BST) and were also observed in the ventromedial nucleus of the hypothalamus. Testosterone target neurons and testosterone target neurons that project to the midbrain were more abundant in the caudal half of the MPN compared to the rostral half. Moreover, male rats had more testosterone target neurons in the caudal MPN than female rats, and the number of testosterone target neurons in the MPN that project to the midbrain was higher in male than in female rats. Male rats also had more testosterone target neurons than females throughout the encapsulated subdivision of the BST. We hypothesize that sex differences in the neuronal connectivity of testosterone target neurons may underly sex specific behavioral responsiveness to androgens.

Animals↗
PubMed1989

Control of feeding movements in the pteropod mollusc, Clione limacina.

(1) The buccal apparatus of the pteropod marine mollusc Clione limacina, isolated together with buccal ganglia, could perform rhythmic feeding movements. Movements of the radula and the hooks (which the Clione inserts into the body of its prey) as well as the electroneurogram of the radular nerve were recorded. Usually one could observe rhythmic radula movements alone, while the hooks were motionless. But sometimes the hooks also performed rhythmic movements which were more or less synchronous with those of the radula. The radula movement cycle consisted of the protraction and the retraction phases, which were occasionally followed by a quiescent phase. Corresponding to each radula movement was a burst of activity in the radular nerve, consisting of the protractor and the retractor components. (2) Isolated buccal ganglia were capable of feeding rhythm generation. Most of the buccal neurons exhibited rhythmic activity correlating with the activity in the radular nerve. According to the phase of activity in the feeding cycle, rhythmic neurons were divided into two groups - the protractor and the retractor ones. The neurons within each of the groups were electrically coupled with each other. The protractor and retractor neurons inhibited each other. (3) Protractor and retractor neurons were extracted from buccal ganglia by means of a microelectrode. Many isolated cells generated slow oscillations of membrane potential and bursts of spikes, the pattern of this activity being similar to that before isolation. (4) A model of the feeding rhythm generator is discussed. It consists of two (protractor and retractor) groups of neurons with mutual inhibitory connections, neurons of each group being endogenous bursters.

Action Potentials↗
PubMed1999

CREB: a message to remember.

The prevailing hypothesis for the formation of long-term memory (LTM) is that introduction of a memory item alters the pattern of existing neuronal connectivity to form a neuronal network that will subserve the information for long-term storage. Modulation of synaptic efficacy is induced by changes in synaptic transmission within selected synapses or alteration in synaptic contacts. These changes are in turn supported by molecules that underlie transmission or synaptic remodeling. It is suggested that modulation of gene expression is needed for LTM formation to overcome the relative short lifetime of proteins in neurons (as compared with enduring memory). One of the most salient results consonant with this hypothesis is that the transcription factor cAMP response element binding (CREB) is involved in the formation of memory in organisms with diverse phylogenetic background from mollusks to mammals. CREB subserves the formation of memories of various types of tasks that utilize different brain structures. Circumstantial evidence is available suggesting that CREB regulates the transcription of genes that subserve LTM. The present review is focused on the CREB protein, its role in memory formation and considers mechanistic models pertaining to CREB action in modulating neuronal networks that underlie LTM.

Animals↗
PubMed1983

Supraspinal connections of neurones in the thoracic spinal cord of the cat: ascending projections and effects of descending impulses.

Single unit electrical activity has been recorded extracellularly from 103 neurones in the thoracic spinal cord of decerebrate cats. The responses of these neurons to electrical stimulation of cutaneous and visceral afferent fibres, their projection through ascending sensory pathways and the effects of descending impulses on the neurones have been studied. Of the 103 neurones recorded, 45 (43.7%) responded only to activation of cutaneous afferent fibres ('Somatic' neurones). Their recording sites were located mainly in laminae II, III and IV of the dorsal horn. The remaining 58 neurones (56.3%) responded to stimulation of cutaneous and visceral afferent fibres ('Viscero-somatic' neurones). Their recording sites were located in laminae I, V, VII and VIII of the grey matter. Sixteen neurones had axons projecting through ascending pathways: 6 were post-synaptic dorsal column cells (PSDC), 2 were spino-cervical tract cells (SCT), 5 projected through the contralateral ventro-lateral funiculus (VLQ) and 3 through the ipsilateral dorso-lateral funiculus (DLF). All PSDC cells were somatic and all VLQ neurones were viscero-somatic. Reversible spinalization of the animals by cold block resulted in a selective increase of the responses of viscero-somatic neurones to cutaneous and visceral C-fibre input. In some viscero-somatic neurones, cold block induced a reduction or abolition of the visceral input suggesting its mediation via supraspinal loops. Electrical stimulation of the ipsilateral DLF evoked non-specific inhibitions of all inputs to viscero-somatic neurones. These results are discussed in relation with the mechanisms of visceral sensation.

Afferent Pathways↗
PubMed1988

Anatomical and functional connections of neurons of the rostral medullary raphe of the rabbit.

Single cell recordings were made from neurons in the rostral medullary raphe (RMR) of the rabbit. The recording sites were ones that had been shown to yield pressor responses from electrical stimulation and by pressure injections of glutamate. Electrical stimulation of the intermediolateral (IML) region of the spinal cord led to antidromic activation of 12 of the 100 cells studied. Eleven of these cells were located in raphe pallidus or raphe magnus, and one cell was located in raphe obscurus. These findings were consistent with the results of horseradish peroxidase (HRP) histochemistry experiments. Injections of HRP into the IML led to heavy cell body labeling in raphe pallidus and raphe magnus, but sparse labeling in raphe obscurus. Cells in the RMR could be orthodromically activated by electrical stimulation of the putative defense area of the periaqueductal (PAG) but not by stimulation of putative defense areas in the hypothalamus. Most of these cells were located in raphe pallidus or raphe magnus. Similarly, HRP injections into raphe pallidus and raphe magnus led to heavy cell body labeling in the PAG but not the hypothalamus; no cell body labeling was found in the PAG when injections were made into raphe obscurus.

Action Potentials↗
PubMed2004

Synaptic connectivity and neuronal morphology: two sides of the same coin.

Neurons often possess elaborate axonal and dendritic arbors. Why do these arbors exist and what determines their form and dimensions? To answer these questions, I consider the wiring up of a large highly interconnected neuronal network, such as the cortical column. Implementation of such a network in the allotted volume requires all the salient features of neuronal morphology: the existence of branching dendrites and axons and the presence of dendritic spines. Therefore, the requirement of high interconnectivity is, in itself, sufficient to account for the existence of these features. Moreover, the actual lengths of axons and dendrites are close to the smallest possible length for a given interconnectivity, arguing that high interconnectivity is essential for cortical function.

Animals↗
PubMed2003

A rat brain slice preserving synaptic connections between neurons of the suprachiasmatic nucleus, organum vasculosum lamina terminalis and supraoptic nucleus.

The organum vasculosum lamina terminalis (OVLT), the suprachiasmatic nucleus (SCN) and the supraoptic nucleus (SON) are three hypothalamic structures involved in the osmotic and circadian control of neurohypophysial secretion. Recent experiments have suggested that interactions between osmotic and circadian factors may be important for homeostasis. The existence of an in vitro slice preparation retaining these nuclei and their interconnections would therefore be useful for the analysis of synaptic interactions. In the rat, the OVLT, SCN and SON are found at increasingly ventral and lateral positions along the rostro-caudal axis, such that conventional 400 microm slices taken in the pure coronal or horizontal planes do not retain all three nuclei. Here we show that horizontal slices cut at angles of 38-42 degrees relative to the dorsal surface of the cortex retain large fractions of the three nuclei. Intracellular recordings revealed membrane properties consistent with those previously published for OVLT, SCN and SON neurons. Moreover, antidromic and synaptic responses evoked by electrical stimulation revealed that extensive axonal projections are retained between these nuclei. Finally, chemical and osmotic stimulation of the OVLT exerted powerful influences on the rate of spontaneous synaptic events in SON neurons. We therefore conclude that angled horizontal hypothalamic slices represent a useful preparation for the analysis of physiological interactions between the OVLT, SCN and SON.

Animals↗
PubMed1997

The morphology and connections of neurons in the gasping centre of adult rats.

Neuronal activities in the intermediate reticular nucleus and adjacent lateral tegmental field are critical for the neurogenesis of the ventilatory pattern of gasping. We report herein the anatomical features of these neurons, their axonal projections and the location of neurons providing afferent inputs. These neuroanatomical evaluations were performed by iontophoretic injection of the tracer Neurobiotin into the region of the intermediate reticular nucleus of the rat. At the site of injection, neurons having soma of 30-50 microns were filled. Labelled axons and terminals were observed in ipsilateral regions which contain neurons having established functions in the control of ventilatory activity. These regions include the nucleus ambiguous and motor nuclei of the hypoglossal and facial nerves. In addition, axonal projections extended to the contralateral region of the intermediate reticular nucleus. From this contralateral region, retrograde tracing revealed projections to the site of injection. Similarly, many ipsilateral regions which received axonal terminals from the region of the intermediate reticular nucleus had reciprocal projections to this region. These anatomical results support the physiological observation that the neurogenesis of gasping involves a synchronized activation of diverse components of the brainstem ventilatory control system.

Animals↗
PubMed2003

The effects of activation of glutamate ionotropic connections of neurons in the sensorimotor cortex in a conditioned reflex.

Changes in conditioned reflex spike activity of neurons in the sensorimotor cortex were studied during microiontophoretic application of agonists and antagonists of glutamate and GABAergic transmission. The results of these experiments showed that the glutamate ionotropic receptors (AMPA and NMDA) of neurons in the sensorimotor cortex were intensely activated by the arrival of a conditioned signal in the cortex. This response included not only large pyramidal neurons of the deep cortical layers, but also the surrounding inhibitory interneurons. The existence of constant tonic inhibitory regulation of the activity of large pyramidal neurons by the surrounding inhibitory cells was demonstrated, along with the active involvement of this inhibition in organizing the excitatory responses of neurons in the sensorimotor cortex during a conditioned reflex.

Action Potentials↗
PubMed2002

Neuroanatomical and neurophysiological consequences of strabismus: changes in the structural and functional organization of the primary visual cortex in cats with alternating fixation and strabismic amblyopia.

In recent years, evidence has accumulated indicating that long-ranging neuronal connections within the primary visual cortex (area 17) mediate the influences of context and experience, possibly also those of expectation. After early onset strabismus, the layout of these connections is massively modified: in strabismic but not in normally raised cats, horizontal connections extend primarily between neurons activated by the same eye. As a possible consequence of the modified circuitry, neuronal synchronization between different ocular dominance domains is also massively reduced. Thus, the inability of strabismics to combine the signals arriving from the two eyes into a single percept may be caused by these structural and functional changes. Strabismic amblyopia is also accompanied by significant modifications of intracortical associational interactions: corresponding to the psychophysical deficits, neurons driven by the normal eye displayed stronger synchronization of their responses than neurons dominated by the amblyopic eye.(1) These data demonstrated for the first time a clear neurophysiological correlate of strabismic amblyopia in area 17. They suggest that - similar to our observations in divergent squinters - at least some of the perceptual deficits of amblyopic patients are due to experience-dependent changes in intracortical circuitry. We analyze this question by combining optical imaging of intrinsic signals with 3-D reconstructions of neuronal circuitry.

Amblyopia↗