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Results for “Neuronal Connectivity”

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At least 631 records · Page 35Linked to original sources
PubMed2001

Improving axonal growth and functional recovery after experimental spinal cord injury by neutralizing myelin associated inhibitors.

Injuries of the spinal cord often result in an irretrievable loss of motor and sensory functions of all body parts situated below the lesion site. Functional recovery is restricted mainly due to the limited regeneration and plasticity of injured axons in the adult central nervous system. Over the last few years different experimental approaches have led to axonal growth and functional benefits in animal models. This review focuses on the effects of the neutralization of myelin-associated neurite growth inhibitors, in particular Nogo-A, using the monoclonal antibody IN-1. Acute mAb IN-1 treatment of adult CNS lesioned rats results in extensive plastic changes of neuronal connections and regenerative fiber growth. In two different lesion paradigms (i.e. pyramidal tract lesion and incomplete spinal cord lesion in adult rats), the mAb IN-1-treated animals always showed a higher degree of recovery in various behavioral tests. These observations, together with electrophysiological results, suggest that neuronal CNS circuits of mAb IN-1-treated animals can be rearranged, and that sprouting and regenerating axons form functionally meaningful connections.

Animals↗
PubMed1999

Brain waves and brain wiring: the role of endogenous and sensory-driven neural activity in development.

Neural activity is critical for sculpting the intricate circuits of the nervous system from initially imprecise neuronal connections. Disrupting the formation of these precise circuits may underlie many common neurodevelopmental disorders, ranging from subtle learning disorders to pervasive developmental delay. The necessity for sensory-driven activity has been widely recognized as crucial for infant brain development. Recent experiments in neurobiology now point to a similar requirement for endogenous neural activity generated by the nervous system itself before sensory input is available. Here we use the formation of precise neural circuits in the visual system to illustrate the principles of activity-dependent development. Competition between the projections from lateral geniculate nucleus neurons that receive sensory input from the two eyes shapes eye-specific connections from an initially diffuse projection into ocular dominance columns. When the competition is altered during a critical period for these changes, by depriving one eye of vision, the normal ocular dominance column pattern is disrupted. Before ocular dominance column formation, the highly ordered projection from retina to lateral geniculate nucleus develops. These connections form before the retina can respond to light, but at a time when retinal ganglion cells spontaneously generate highly correlated bursts of action potentials. Blockade of this endogenous activity, or biasing the competition in favor of one eye, results in a severe disruption of the pattern of retinogeniculate connections. Similar spontaneous, correlated activity has been identified in many locations in the developing central nervous system and is likely to be used during the formation of precise connections in many other neural systems. Understanding the processes of activity-dependent development could revolutionize our ability to identify, prevent, and treat developmental disorders resulting from disruptions of neural activity that interfere with the formation of precise neural circuits.

Aging↗
PubMed2002

Rho proteins, mental retardation and the cellular basis of cognition.

For several decades, it has been known that mental retardation (MR) is associated with abnormalities in dendrites and dendritic spines. The recent cloning of seven genes that cause nonspecific MR when mutated provides important insights in the cellular mechanisms that result in the dendritic abnormalities associated with MR. Three of the encoded proteins, oligophrenin 1, PAK3 and alpha PIX, interact directly with Rho GTPases. Rho GTPases are key signaling proteins that integrate extracellular and intracellular signals to orchestrate coordinated changes in the actin cytoskeleton essential for directed neurite outgrowth and the regulation of synaptic connectivity. Although many details of the cell biology of Rho signaling in the CNS are still unclear, a picture is unfolding showing how mutations that alter Rho signaling result in abnormal neuronal connectivity and deficient cognitive functioning in humans. Conversely, these findings illuminate the cellular mechanisms underlying normal cognitive function.

Actins↗
PubMed2002

Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system.

Neuronal connections are made during embryonic development with astonishing precision to ultimately form the physical basis for the central nervous system's main capacity: information processing. Over the past few decades, much has been learned about the general principles of axon guidance. A key finding to emerge is that extracellular cues play decisive roles in establishing the connections. One family of such cues, the semaphorin proteins, was first identified as repellents for navigating axons during brain wiring. Recent studies have implicated these molecules in many other processes of neuronal development, including axonal fasciculation, target selection, neuronal migration, and dendritic guidance, as well as in the remodeling and repair of the adult nervous system. It appears that responding neuronal processes sense these semaphorin signals by a family of transmembrane molecules, namely the plexins, even though neuropilins were also found to be required for mediating the interaction between plexins and class 3 semaphorins. Our understanding of the intracellular signaling machinery linking the receptors to the cytoskeleton machinery is still incomplete, but several molecules have been implicated in mediating or modulating semaphorin-induced responses. Adding to the complexity of semaphorin biology, new findings implicate semaphorins in functioning not only as signaling ligands, but also as signal-transducing receptors. Thus, semaphorins may serve as important probes for exploring the mechanisms of intercellular communication during the development and function of the nervous system.

Animals↗
PubMed2006

Mutations in the K+/Cl- cotransporter gene kazachoc (kcc) increase seizure susceptibility in Drosophila.

During a critical period in the developing mammalian brain, there is a major switch in the nature of GABAergic transmission from depolarizing and excitatory, the pattern of the neonatal brain, to hyperpolarizing and inhibitory, the pattern of the mature brain. This switch is believed to play a major role in determining neuronal connectivity via activity-dependent mechanisms. The GABAergic developmental switch may also be particularly vulnerable to dysfunction leading to seizure disorders. The developmental GABA switch is mediated primarily by KCC2, a neuronal K+/Cl- cotransporter that determines the intracellular concentration of Cl- and, hence, the reversal potential for GABA. Here, we report that kazachoc (kcc) mutations that reduce the level of the sole K+/Cl- cotransporter in the fruitfly Drosophila melanogaster render flies susceptible to epileptic-like seizures. Drosophila kcc protein is widely expressed in brain neuropil, and its level rises with developmental age. Young kcc mutant flies with low kcc levels display behavioral seizures and demonstrate a reduced threshold for seizures induced by electroconvulsive shock. The kcc mutation enhances a series of other Drosophila epilepsy mutations indicating functional interactions leading to seizure disorder. Both genetic and pharmacological experiments suggest that the increased seizure susceptibility of kcc flies occurs via excitatory GABAergic signaling. The kcc mutants provide an excellent model system in which to investigate how modulation of GABAergic signaling influences neuronal excitability and epileptogenesis.

Animals↗
PubMed1980

Afferent and efferent connections of cat omnipause neurons.

Afferent and efferent connections of behaviorally identified omnipause neurons involved in saccadic eye movements were investigated electrophysiologically in cats anesthetized with ketamine hydrochloride. Pause cells were polysynaptically excited by electrical stimulation of the optic chiasm (mean latency = 8.3 ms), the visual cortex (mean latency = 7.3 ms), and the superior colliculus (mean latency = 2.6 ms). Bilateral removal of either the visual cortex or the superior colliculus 1 week prior to the experiment abolished optic chiasm responses. Pause cells were antidromically activated by electrical stimulation of the prerubral fields (mean latency = 1.1 ms), or the pontine and medullary reticular formation (mean latency = 1.0 ms). Frequently, the same pause cell was antidromically excited by prerubral and pontine or medullary reticular stimulation indicating that its axon was branched. The spontaneous discharge of pause cells was polysynaptically suppressed by sustained galvanic polarization of either labyrinth, or by multiple shock stimulation in the reticular formation.

Animals↗
PubMedDate not supplied

The correlation grid: analysis of synchronous spiking in multi-dimensional spike train data and identification of feasible connection architectures.

This paper presents a visualization technique specifically designed to support the analysis of synchronous firings in multiple, simultaneously recorded, spike trains. This technique, called the correlation grid, enables investigators to identify groups of spike trains, where each pair of spike trains has a high probability of generating spikes approximately simultaneously or within a constant time shift. Moreover, the correlation grid was developed to help solve the following reverse problem: identification of the connection architecture between spike train generating units, which may produce a spike train dataset similar to the one under analysis. To demonstrate the efficacy of this approach, results are presented from a study of three simulated, noisy, spike train datasets. The parameters of the simulated neurons were chosen to reflect the typical characteristics of cortical pyramidal neurons. The schemes of neuronal connections were not known to the analysts. Nevertheless, the correlation grid enabled the analysts to find the correct connection architecture for each of these three data sets.

Action Potentials↗
PubMed1987

Thalamocortical and thalamo-amygdaloid projections from the parvicellular division of the posteromedial ventral nucleus in the cat.

Projections from the parvicellular division of the posteromedial ventral thalamic nucleus (VPMpc) of the cat were examined. After injection of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) into the VPMpc, both anterogradely labeled axon terminals and retrogradely labeled neuronal cell bodies were found ipsilaterally in three discrete regions of the cerebral cortex, i.e., in the orbital cortex, caudoventral part of the infralimbic cortex, and medial part of the fundus of the posterior rhinal sulcus (perirhinal area); in the subcortical regions, anterogradely labeled axon terminals were seen ipsilaterally in the rostrodorsal part of the lateral amygdaloid nucleus. Neuronal connections between these VPMpc-recipient regions were further verified by injecting WGA-HRP into each of the three cortical and the lateral amygdaloid regions. After injection of WGA-HRP into each of the three cortical regions, labeled neuronal cell bodies and axon terminals were seen ipsilaterally in the VPMpc, especially in its medial part, and in the other two of the three VPMpc-recipient cortical regions. In the rostrodorsal part of the lateral amygdaloid nucleus, both axon terminals and neuronal cell bodies were labeled after WGA-HRP injection into the perirhinal area, and only axon terminals were labeled after WGA-HRP injection into the orbital cortex, but no labeling was observed after WGA-HRP injection into the infralimbic cortex. After injection of WGA-HRP into the rostrodorsal portion of the lateral amygdaloid nucleus, both axon terminals and neuronal cell bodies were labeled ipsilaterally in the perirhinal area and the ectorhinal area, and only neuronal cell bodies were labeled ipsilaterally in the VPMpc (especially in its medial part) and orbital cortical region; no labeling was observed in the infralimbic cortex. The present results indicate that the VPMpc of the cat is connected reciprocally with the orbital, infralimbic, and perirhinal cortical regions on the ipsilateral side, that the three VPMpc-recipient cortical regions are reciprocally connected with each other, that the VPMpc sends fibers ipsilaterally to the rostrodorsal part of the lateral amygdaloid nucleus, which may relay information from the VPMpc to the perirhinal cortical area, and that the VPMpc-recipient area in the lateral amygdaloid nucleus receives cortical fibers from the orbital and perirhinal cortical regions.

Amygdala↗
PubMedDate not supplied

Visual function in regenerating teleost retina following cytotoxic lesioning.

Teleost fish retinas can regenerate in vivo in adulthood. Retinal and visual function was assessed in adult goldfish following comprehensive retinal destruction by intraocular injection of ouabain. Electroretinograms (ERGs) and the dorsal light reflex (DLR) were used to evaluate the return of visual function. ERGs were detectable in regenerating eyes 50 to 70 days following ouabain injection. Amplitudes of both a- and b-waves increased steadily through day 210 following ouabain treatment, at which time a-wave amplitude was 90% and b-wave amplitude approached 50% of the contralateral control eye. The progressive gain observed in the a-wave was attributed to photoreceptor regeneration. The increase in b-wave amplitude was attributed to an increase in the number of inner nuclear layer cells and the number and efficacy of neuronal connections to or within the inner retina. The photopic spectral sensitivity of the b-wave in regenerating retina closely matched the intrafish control retina, suggesting that the relative numbers of cone photoreceptors was normal in regeneration. The recovery of the DLR (indicated by improved postural balance during regeneration) paralleled electrophysiological gains during retinal regeneration. Fish displayed a marked longitudinal body imbalance toward the control eye following retinal destruction. Improvement in equilibrium was correlated with increasing b-wave amplitudes. When the b-wave reached 50% of control amplitude (30 weeks), normal posture was restored. The return of the ERG indicates that photoreceptors and their synaptic connections must be functional in regenerating retina. Failure of the retina to regenerate produced an abnormal DLR that persisted through 30 weeks and ERGs were not measurable. The return of normal equilibrium indicates that the regenerating retina can establish central connections to the brain, and that the regenerated connections can mediate functional visual behavior.

Animals↗
PubMed1998

A cross-interval spike train analysis: the correlation between spike generation and temporal integration of doublets.

A stochastic spike train analysis technique is introduced to reveal the correlation between the firing of the next spike and the temporal integration period of two consecutive spikes (i.e., a doublet). Statistics of spike firing times between neurons are established to obtain the conditional probability of spike firing in relation to the integration period. The existence of a temporal integration period is deduced from the time interval between two consecutive spikes fired in a reference neuron as a precondition to the generation of the next spike in a compared neuron. This analysis can show whether the coupled spike firing in the compared neuron is correlated with the last or the second-to-last spike in the reference neuron. Analysis of simulated and experimentally recorded biological spike trains shows that the effects of excitatory and inhibitory temporal integration are extracted by this method without relying on any subthreshold potential recordings. The analysis also shows that, with temporal integration, a neuron driven by random firing patterns can produce fairly regular firing patterns under appropriate conditions. This regularity in firing can be enhanced by temporal integration of spikes in a chain of polysynaptically connected neurons. The bandpass filtering of spike firings by temporal integration is discussed. The results also reveal that signal transmission delays may be attributed not just to conduction and synaptic delays, but also to the delay time needed for temporal integration.

Action Potentials↗
PubMed1997

Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration.

Irregular firing patterns are observed in most central neurons in vivo, but their origin is controversial. Here, we show that two types of inhibitory neurons in the cerebellar cortex fire spontaneously and regularly in the absence of synaptic input but generate an irregular firing pattern in the presence of tonic synaptic inhibition. Paired recordings between synaptically connected neurons revealed that single action potentials in inhibitory interneurons cause highly variable delays in action potential firing in their postsynaptic cells. Activity in single and multiple inhibitory interneurons also significantly reduces postsynaptic membrane time constant and input resistance. These findings suggest that the time window for synaptic integration is a dynamic variable modulated by the level of tonic inhibition, and that rate coding and temporal coding strategies may be used in parallel in the same cell type.

Action Potentials↗
PubMed2001

Orientation preference patterns in mammalian visual cortex: a wire length minimization approach.

In the visual cortex of many mammals, orientation preference changes smoothly along the cortical surface, with the exception of singularities such as pinwheels and fractures. The reason for the existence of these singularities has remained elusive, suggesting that they are developmental artifacts. We show that singularities reduce the length of intracortical neuronal connections for some connection rules. Therefore, pinwheels and fractures could be evolutionary adaptations keeping cortical volume to a minimum. Wire length minimization approach suggests that interspecies differences in orientation preference maps reflect differences in intracortical neuronal circuits, thus leading to experimentally testable predictions. We discuss application of our model to direction preference maps.

Animals↗
PubMed2002

Serotonin sets the day state in the neurons that control coupling between the optic lobe circadian pacemakers in the cricket Gryllus bimaculatus.

The bilaterally paired optic lobe circadian pacemakers of the cricket Gryllus bimaculatus mutually exchange photic and circadian information to keep their activity synchronized. The information is mediated by a neural pathway, consisting of the so-called medulla bilateral neurons, connecting the medulla areas of the two optic lobes. We investigated the effects of serotonin on the neural activity in this coupling pathway. Spontaneous and light-induced electrical activity of the neurons in the coupling pathway showed daily variations, being more intense during the night than the day. Microinjection of serotonin or a serotonin-receptor agonist, quipazine, into the optic lobe caused a dose- and time-dependent inhibition of spontaneous and light-induced responses, mimicking the day state. The amount of suppression was greater and the recovery from the suppression occurred faster during the night. Application of metergoline, a non-selective serotonin-receptor antagonist, increased spontaneous activity and light-evoked responses during both the day and the night, with higher effect during the day. In addition, metergoline effectively attenuated the effects of serotonin. These facts suggest that in the cricket's optic lobe, serotonin is released during the daytime and sets the day state in the neurons regulating coupling between the bilaterally paired optic lobe circadian pacemakers.

Animals↗
PubMed1989

[Effects of death of a single neuron on the functional organization of the neuronal ensemble in the leech].

The reaction of leech nervous system after elimination of individual mechanosensory neuron by intracellular Pronase injection were studied. In the motor neurons connected with killed cells at 14-90th days after the operation there were the changes of the resting membrane potential and amplitude of postsynaptic potentials developed by the stimulation of mechanosensory neuron. It is suggested that the leech nervous system serves as the dynamic formation depending on changes of neuronal ensemble structure.

Animals↗
PubMed2004

Labeling neurons in vivo for morphological and functional studies.

Increasingly sophisticated strategies for labeling cells in vivo are providing unprecedented opportunities to study neurons in living animals. Transgenic expression of genetically encoded reporters enables us to monitor changes in neuronal activity in response to sensory stimuli, and the labeling of single neurons with fluorescent proteins allows the dynamics of neuronal connectivity to be observed in transgenic animals over periods ranging from minutes to months. Advances in transient labeling techniques such as viral infection and electroporation provide a rapid means by which to analyze neuronal gene function in vivo. These new approaches to labeling, manipulating and imaging neurons in intact organisms are transforming the way in which the nervous system is studied.

Animals↗
PubMed2005

Rho proteins, mental retardation and the neurobiological basis of intelligence.

For several decades it has been known that mental retardation is associated with abnormalities in dendrites and dendritic spines. The recent cloning of eight genes which cause nonspecific mental retardation when mutated, provides an important insight into the cellular mechanisms that result in the dendritic abnormalities underlying mental retardation. Three of the encoded proteins, oligophrenin1, PAK3 and alphaPix, interact directly with Rho GTPases. Rho GTPases are key signaling proteins which integrate extracellular and intracellular signals to orchestrate coordinated changes in the actin cytoskeleton, essential for directed neurite outgrowth and the generation/rearrangement of synaptic connectivity. Although many details of the cell biology of Rho signaling in the CNS are as yet unclear, a picture is unfolding showing how mutations that cause abnormal Rho signaling result in abnormal neuronal connectivity which gives rise to deficient cognitive functioning in humans.

Acute-Phase Proteins↗
PubMed1994

In vivo neuronal synthesis and axonal transport of Kunitz protease inhibitor (KPI)-containing forms of the amyloid precursor protein.

We have shown previously that the amyloid precursor protein (APP) is synthesized in retinal ganglion cells and is rapidly transported down the axons, and that different molecular weight forms of the precursor have different developmental time courses. Some APP isoforms contain a Kunitz protease inhibitor (KPI) domain, and APP that lacks the KPI domain is considered the predominant isoform in neurons. We now show that, among the various rapidly transported APPs, a 140-kDa isoform contains the KPI domain. This APP isoform is highly expressed in rapidly growing retinal axons, and it is also prominent in adult axon endings. This 140-kDa KPI-containing APP is highly sulfated compared with other axonally transported isoforms. These results show that APP with the KPI domain is a prominent isoform synthesized in neurons in vivo, and they suggest that the regulation of protease activity may be an important factor during the establishment of neuronal connections.

Amyloid beta-Protein Precursor↗
PubMed1990

[Use of fluorescent carbocyanine dyes in the study of the organization of the pathways in autopsy material of the human brain].

Our report provides evidence that fluorescent carbocyanine dyes (diI and diO) can be used in experimental anatomical studies of the fixed autopsy human brain. The dyes transported in both anterograde and retrograde directions, providing labeling of axons with collaterals and neurons including dendrites. To study the retrograde labeling of pyramidal neurons and anterogradely labeling of afferent fibers in human motor cortex, we applied diI and diO to the white matter, I and III layers of cortex. During 2 months there was no evidence of passive diffusion from labeled fibers and neurons to other neurons or glia. This method will be useful for identifying alterations of neuronal connections associated with neurological and psychiatric disorders.

Aged↗