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Neuronal control of mammalian vocalization, with special reference to the squirrel monkey.

Squirrel monkey vocalization can be considered as a suitable model for the study in humans of the neurobiological basis of nonverbal emotional vocal utterances, such as laughing, crying, and groaning. Evaluation of electrical and chemical brain stimulation data, lesioning studies, single-neurone recordings, and neuroanatomical tracing work leads to the following conclusions: The periaqueductal gray and laterally bordering tegmentum of the midbrain represent a crucial area for the production of vocalization. This area collects the various vocalization-triggering stimuli, such as auditory, visual, and somatosensory input from diverse sensory-processing structures, motivation-controlling input from some limbic structures, and volitional impulses from the anterior cingulate cortex. Destruction of this area causes mutism. It is still under dispute whether the periaqueductal region harbors the vocal pattern generator or merely couples vocalization-triggering information to motor-coordinating structures further downward in the brainstem. The periaqueductal region is connected with the phonatory motoneuron pools indirectly via one or several interneurons. The nucleus retroambiguus represents a crucial relay station for the laryngeal and expiratory component of vocalization. The articulatory component reaches the orofacial motoneuron pools via the parvocellular reticular formation. Essential proprioceptive feedback from the larynx and lungs enter the vocal-controlling network via the solitary tract nucleus.

Animals↗

Hemispheric asymmetries in cognitive modeling: connectionist modeling of unilateral visual neglect.

Neglect is an acquired cognitive disorder characterized by a lack of processing of one side of a stimulus or representational space. There are hemispheric asymmetries in its cause and in its effects, but implemented computational models of neglect have tended not to incorporate this fact. The authors report a series of neural network simulations of the line-bisection task. They test the hypothesis that simple, neuroanatomically realistic principles of connectivity in the nervous system can produce emergent behaviors that capture a wide range of quantitative and qualitative data observed in neglect patients presenting with general visuospatial neglect. They demonstrate that exploring low-level architectural principles in implemented computational models is both a productive avenue of research and offers the most parsimonious explanations of behaviors observed in patients.

Brain↗

Planarian Gtsix3, a member of the Six/so gene family, is expressed in brain branches but not in eye cells.

Six/sine oculis (Six/so) class genes, with representatives in vertebrates and invertebrates, include members with key developmental roles in the anterior part of the central nervous system (CNS) and eye. Having characterized the role of the first planarian gene of the Six/so family in eye development, we attempted to identify novel genes of this family related to the platyhelminth eye genetic network. We isolated a new Six/so gene in the planarian Girardia tigrina, Gtsix-3, which belongs to the Six3/6 class. Whole mount in situ hybridization revealed Gtsix3 expression in a stripe surrounding the cephalic ganglia in adults. This spatial pattern corresponds to the cephalic branches, the nerve cells that connect the CNS with the marginal sensory organs located continuously at the edge of the head. During head regeneration, Gtsix-3 shows delayed activation compared to other head genes, with an initial two spot pattern that later evolves to a continuous lateral expression in the new regenerated cephalic ganglia with a final reduction to the adult pattern. However, Gtsix-3 is not activated in tail regeneration and no eye expression is observed at any regenerative stage. These findings provide a new marker for the developing anterior nervous system and evidence the complexity of planarian brain.

Amino Acid Sequence↗

Gustatory processing: a dynamic systems approach.

Recent gustatory studies have provided a growing body of evidence that taste processing is dynamic and distributed, and the taste system too complex to be adequately described by traditional feed-forward models of taste coding. Current research demonstrates that neuronal responses throughout the gustatory neuroaxis are broad, variable and temporally structured, as a result of the fact that the taste network is extensive and heavily interconnected, containing modulatory pathways, many of which are reciprocal. Multimodal influences (e.g. olfactory and somatosensory) and effects of internal state (e.g. attention and expectation), shown in both behavioral and neuronal responses to taste stimuli, add further complexity to neural taste responses. Future gustatory research should extend to more brain regions, incorporate more connections, and analyze behaviors and neuronal responses in both time- and state-dependent manners.

Animals↗

Plasticity in single neuron and circuit computations.

Plasticity in neural circuits can result from alterations in synaptic strength or connectivity, as well as from changes in the excitability of the neurons themselves. To better understand the role of plasticity in the brain, we need to establish how brain circuits work and the kinds of computations that different circuit structures achieve. By linking theoretical and experimental studies, we are beginning to reveal the consequences of plasticity mechanisms for network dynamics, in both simple invertebrate circuits and the complex circuits of mammalian cerebral cortex.

Animals↗

On the cellular and network bases of epileptic seizures.

The highly interconnected networks of the mammalian forebrain can generate a wide variety of synchronized activities, including those underlying epileptic seizures, which often appear as a transformation of otherwise normal brain rhythms. The cerebral cortex and hippocampus are particularly prone to the generation of the large, synchronized bursts of activity underlying many forms of seizures owing to strong recurrent excitatory connections, the presence of intrinsically burst-generating neurons, ephaptic interactions among closely spaced neurons, and synaptic plasticity. The simplest form of epileptiform activity in these structures is the interictal spike, a synchronized burst of action potentials generated by recurrent excitation, followed by a period of hyperpolarization, in a localized pool of pyramidal neurons. Seizures can also be generated in response to a loss of balance between excitatory and inhibitory influences and can take the form of either tonic depolarizations or repetitive, rhythmic burst discharges, either as clonic or spike-wave activity, again mediated both by intrinsic membrane properties and synaptic interactions. The interaction of the cerebral cortex and the thalamus, in conjunction with intrathalamic communication, can also generate spike waves similar to those occurring during human absence seizure discharges. Although epileptic syndromes and their causes are diverse, the cellular mechanisms of seizure generation appear to fall into only two categories: rhythmic or tonic "runaway" excitation or the synchronized and rhythmic interplay between excitatory and inhibitory neurons and membrane conductances.

Animals↗

Traveling waves of excitation in neural field models: equivalence of rate descriptions and integrate-and-fire dynamics.

Field models provide an elegant mathematical framework to analyze large-scale patterns of neural activity. On the microscopic level, these models are usually based on either a firing-rate picture or integrate-and-fire dynamics. This article shows that in spite of the large conceptual differences between the two types of dynamics, both generate closely related plane-wave solutions. Furthermore, for a large group of models, estimates about the network connectivity derived from the speed of these plane waves only marginally depend on the assumed class of microscopic dynamics. We derive quantitative results about this phenomenon and discuss consequences for the interpretation of experimental data.

Animals↗

Hypotheses on mnemonic information processing by the brain.

From a neuropsychological point of view, hypotheses are offered on the possible action of the brain in the processing of mnemonic information for long-term storage (or for retrieval of long-term stored information). It is argued that strict relations between damage of circumscribed brain structures and amnesia, as they have been suggested in recent case reports, are questionable for several reasons: Firstly, the involved regions differ between cases; secondly, there is some counter-evidence from other cases in which similar neuronal damage failed to result in lasting amnesic disturbances; thirdly, it is hypothesized that even from circumscribed brain damage it is not justifiable to conclude that the lesioned structure is solely or principally responsible for the observed mnemonic changes, as the brain acts in an integrative way, that is, on the basis of a wide-spread network of neuronal information processing. On the basis of these and related arguments, hypotheses and models on mnemonic information processing in the intact and in the damaged brain are derived. With these hypotheses even the frequent observation of interindividual differences in mnemonic information processing finds a possible explanation which is in conformity to known anatomical circuits and connections and to principles of neuronal coding.

Amnesia↗

The challenges and rewards of integrating diverse neuroscience information.

The design of database models and schemas for storing, cross-referencing, and retrieving neuroscience information faces issues that are similar but more complex than most of the other biomedical disciplines, such as genomics and proteonomics. Specifically, the visualization and manipulation of very large and diverse image data, such as digital brain atlases and functional magnetic resonance images, play a unique role in neuroscience while much of the associated information is textually recorded. Nongraphical information can include the annotation of large brain structures ranging from anatomical regions to intracellular structures, the description of cellular functional properties, and their various interrelationships, such as fiber connections. It is necessary that the heterogeneous and distributed types of data be cross-referenced to each other so that this diverse information can be efficiently retrieved, shared, and exchanged among the different neuroscientific disciplines. Continued advances in computers and Internet technologies appear to indicate that increasingly large data sets will be maintained on local or regional file servers and that informational interoperability will be achieved using a networked information system infrastructure. The authors and others have proposed and implemented models of semantically organized information systems that utilize centrally stored and highly structured archival information to index, cross-reference, and retrieve diverse, Web-based data sets.

Brain↗

Quantitative morphological analysis of embryonic cockroach (Periplaneta americana) brain neurons developing in vitro.

Neurons dissociated from the brain of embryonic cockroaches (Periplaneta americana) can be maintained in culture for several weeks. The survival as well as the progressive organization of the neurons into a complex network was studied during a 5-week period under different culture conditions. About 10% of the dissociated cells adhered to the culture dish. This figure remained constant throughout the culture. The cell diameter ranged from 10 to 20 microns and did not change significantly over time in culture. Whereas only a few cells exhibited neurites at the start of the culture, the number of cells exhibiting neurites increased to reach about 99% after 2 weeks. The different cells were then connected to each other, forming a network, which became more and more complex. The number of cells per cluster as well as the length and the diameter of the "connectives" that linked the different clusters were found to increase with time. The morphology of individual neurons within the network was visualized after intracellular injection of biocytin. Labeling with antibodies raised against serotonin or GABA indicated that neurons were able to differentiate and to acquire specific neurotransmitter fates. The serotonergic phenotype was found to appear progressively throughout the culture, in parallel with the formation of the network. Cell density, addition of fetal calf serum, and ecdysone were shown to influence the development of the network.

Animals↗

Progress and perspectives in computational neuroanatomy.

The tremendous increase in processing power of personal computers has recently allowed the construction of highly sophisticated models of neuronal function and behavior. Anatomy plays a fundamental role in supporting and shaping nervous system activity, yet to date most details of such a role have escaped the efforts of experimental and theoretical neuroscientists, mainly because of the problem's complexity. When accurate cellular morphologies are included in electrophysiological computer simulations, quantitative and qualitative effects of dendritic structure on firing properties can be extensively characterized. Complete models of dendritic morphology can be implemented to allow the computer generation of virtual neurons that model the anatomical characteristics of their real counterparts to a great degree of approximation. From a restricted and already available experimental database, stochastic and statistical algorithms can create an unlimited number of non-identical virtual neurons within several mammalian morphological classes, storing them in a compact and parsimonious format. When modeled neurons are distributed in three-dimensional and biologically plausible rules governing axonal navigation and connectivity are added to the simulations, entire portions of the nervous system can be "grown" as anatomically realistic neural networks. These computational constructs are useful to determine the influence of local geometry on system neuroanatomy, and to investigate systematically the mutual interactions between anatomical parameters and electrophysiological activity at the network level. A detailed computer model of a "virtual brain" that was truly equivalent to the biological structure could in principle allow scientists to carry out experiments that could not be performed on real nervous systems because of physical constraints. The computational approach to neuroanatomy is just at its beginning, but has a great potential to enhance the intuition of investigators and to aid neuroscience education. Anat Rec (New Anat): 257:195-207, 1999.

Animals↗

Shared genetic architecture between major depression and intrinsic brain functional connectome organization.

BACKGROUND: Major depression (MD) is increasingly understood as a disorder characterized by widespread abnormalities in intrinsic brain functional network organization. Although both MD and brain functional connectome architecture are highly heritable, the genetic architecture underlying their relationship remains poorly characterized. METHODS: We integrated genome-wide association studies of MD with 191 ICA-based resting-state functional connectome traits to investigate their shared genetic architecture. These traits captured intrinsic connectome organization across amplitude, functional connectivity, and global connectivity domains. Cross-trait genetic analyses were used to assess pleiotropic overlap between traits. Locus-level and gene-based analyses integrating multi-omics evidence were performed to characterize the biological relevance of shared genetic signals. RESULTS: We identified significant genetic overlap between MD and 148 of 191 brain functional connectome traits. Cross-trait analyses revealed widespread shared genetic signals organized into 627 genomic loci across amplitude, functional connectivity, and global connectivity measures. Among these, 193 loci showed evidence consistent with shared causal variants based on colocalization analyses. Gene-level integration mapped these loci to 1459 protein-coding genes (390 unique genes). Multi-layer prioritization identified 17 high-confidence genes supported by convergent genomic, transcriptomic, and proteomic evidence, with enrichment in neurodevelopmental and lipid-related metabolism pathways. CONCLUSIONS: This study provides a multi-scale characterization of the shared genetic architecture between MD and intrinsic brain functional connectome organization, revealing that shared genetic signals between MD and brain functional systems are distributed across multiple functional levels and converge at the molecular level.

Connectome↗

Lymphatic vessels gain access to cerebrospinal fluid through unique association with olfactory nerves.

BACKGROUND: Physiological studies suggest that a major portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. Especially important is CSF transport through the cribriform plate in association with the olfactory nerves. This study examined the anatomical connections that link the CSF and extracranial lymphatics at the base of the brain. METHODS AND RESULTS: The contrast agent, Yellow Microfil, was infused into the cranial sub-arachnoid compartment of 2- to 7-day-old lambs postmortem. In some animals, blue Microfil was perfused into the carotid arteries. Yellow Microfil was observed in extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. Since little of the contrast agent was present within the interstitium of the olfactory submucosa, there appeared to be direct continuity between the subarachnoid space, the perineurial spaces of the olfactory nerve fibers that penetrated the cribriform plate, and the lumens of the lymphatic vessels within the olfactory submucosa. Lymphatics encircled the olfactory nerves at the level of the emerging nerve rootlets (in many cases providing the outer limit of the perineurial space) and then dispersed freely in the submucosa at greater distance from the crib-riform plate. These vessels converged into larger collecting ducts that emptied into various lymph nodes in the head and neck. CONCLUSIONS: Lymphatic vessels gain access to the brain extracellular fluid (CSF) in an unusual anatomical association with the olfactory nerves external to the cranial vault. This study highlights the important role played by lymphatic vessels in CSF absorption.

Animals↗

Temporal correlations in stochastic networks of spiking neurons.

The determination of temporal and spatial correlations in neuronal activity is one of the most important neurophysiological tools to gain insight into the mechanisms of information processing in the brain. Its interpretation is complicated by the difficulty of disambiguating the effects of architecture, single-neuron properties, and network dynamics. We present a theory that describes the contribution of the network dynamics in a network of "spiking" neurons. For a simple neuron model including refractory properties, we calculate the temporal cross-correlations in a completely homogeneous, excitatory, fully connected network in a stable, stationary state, for stochastic dynamics in both discrete and continuous time. We show that even for this simple network architecture, the cross-correlations exhibit a large variety of qualitatively different properties, strongly dependent on the level of noise, the decay constant of the refractory function, and the network activity. At the critical point, the cross-correlations oscillate with a frequency that depends on the refractory properties or decay exponentially with a diverging damping constant (for "weak" refractory properties). We also investigate the effect of the synaptic time constants. It is shown that these time constants may, apart from their influence on the asymmetric peak arising from the direct synaptic connection, also affect the long-term properties of the cross-correlations.

Action Potentials↗

[The neurobiology of pain].

The nociceptive system enables us to respond in time to external threats that otherwise would produce tissue damage. By monitoring tissue composition the system also contributes to bodily homeostasis. Nociceptors signal mechanical stress, extreme temperatures, cell injury and inflammation. Powerful modulation of nociceptive signals occurs in the spinal dorsal horn, so that their further transmission to the brain can be enhanced or inhibited. A vast array of transmitters and receptors are responsible for complex synaptic interactions in the dorsal horn. Synaptic plasticity alters neuronal excitability for hours to months (years?), contributing to hyperalgesia and chronic pain. Descending monoaminergic connections from the brain stem can inhibit or facilitate the signal transmission from nociceptors. These systems are partly controlled by ascending signals from the dorsal horn, partly by descending connections from amygdala, hypothalamus and the cerebral cortex. The latter are thought to contribute to context-dependent pain modulation. The subjective experience of pain correlates with increased activity in a cortical network including the insula, the cingulate gyrus and some other areas. The activity of the network is also positively correlated with expectation of pain, and negatively correlated with expectation of pain relief--independent of nociceptor stimulation.

Central Nervous System↗

[Neurobiology of learning--the basis of an alteration process].

In contrast to the opinion that prevailed in the 1980es, there is now increasing evidence that the plasticity of the human brain, i. e. its remarkable ability to adapt to and change with experience, is, under normal conditions, a lifelong phenomenon. Representations of the environment are associated with activations and biochemical modifications in neuronal networks, which will be stabilized, modified or will wither in the course of cumulated experience. The capability to modify the biochemistry of synapses as well as the growth and change in terms of rewiring of synapses, dendritic branching and glial cell proliferation via the dialogue of synapses and genes, results in specific changes in neuronal connectivity and function. On the neurotransmitter level, glutamate and gamma-amino-butyric acid (GABA) as well as dopamine and serotonin, but also endorphin and encephalin, have a key position in this context. These neurotransmitter systems modulate neuronal plasticity on the neuronal level; on the behavioural level they influence affect, emotion, positive motivation and the correct evaluation of environmental stimuli. Experience, action as well as learning and memory are influenced by these systems. A basic thesis of this paper is that these mechanisms are involved in neuronal plasticity and that learning and memory are thus not only used and reused in structuring the CNS during the initial establishment of connections in the immature brain, in lifelong memory consolidation or the rewiring after brain damage, but can also be used to mould experience, learning und behaviour during psychotherapy and rehabilitation in adults.

Brain↗

Methylene blue supravital staining: an evaluation of its applicability to the mammalian brain and pineal gland.

Methylene blue supravital staining of mammalian brain reveals typical staining patterns in different brain regions. Within the cerebellum of the mouse, the dye showed a peculiar affinity for the somata and the axons of Purkinje cells. Additionally, large polymorphic neurons characterized by long descending axons were detected within the granular layer and the white matter. These cells might represent another type of projection neuron. In the stratum pyramidale and stratum oriens of the murine hippocampus, a subpopulation of non-pyramidal cells, i.e. intrinsic interneurons, were selectively stained. Additionally, a labelling of perineuronal nets of extracellular matrix covering single cells could be achieved; this phenomenon might be due to the occurrence of strong anionic residues which attract the cationic dye. Therefore, perineuronal nets might also trap other cations and play an important role in the control of cell excitability. The electron microscopic investigation revealed drop-like dye accumulations within the cytoplasm and a staining of material at the site of the plasma membrane. Throughout the pineal gland, a network of a subpopulation of polymorphic cells with manifold long processes could be visualized. Syncytial connections of cells seemed to occur. The oxygen-dependent selective staining is probably functionally connected with the generation of oxygen radicals and subsequent oxidative stress for the cells. This reaction indicates a certain vulnerability to hypoxia; therefore, the intracellular dye-uptake might be interpreted as an early sign of metabolic disturbance.

Animals↗

Anticonvulsant A(1) receptor-mediated adenosine action on neuronal networks in the brainstem-spinal cord of newborn rats.

Membrane potential of ventral respiratory group neurons as well as inspiratory-related cranial (hypoglossal) and spinal (C(1)-Th(4)) nerve activities were analysed in brainstem-spinal cord preparations from neonatal rats. Block of Cl(-)-mediated inhibition with bicuculline (plus strychnine) affected neither rhythmic depolarizations nor spike discharge in 23 of 30 ventral respiratory group cells. In the other seven neurons, block of inhibitory postsynaptic potentials evoked pronounced depolarizations and spike discharge that was synchronous with seizure-like spinal nerve activity. Respiratory hypoglossal nerve activity persisted after transection at the spinomedullary junction, whereas spinal rhythm was blocked. After transection, the moderate bicuculline-evoked seizure-like perturbation of hypoglossal nerve activity was abolished and rhythmic ventral respiratory group neuron activity was not disturbed, whereas epileptiform discharge persisted in spinal nerves. The seizure-like nerve activity and depolarization of the minor subpopulation of perturbed ventral respiratory group neurons were reversed by either adenosine or the A(1) adenosine receptor agonist 2-chloro-N(6)-cyclopentyladenosine. The A(2) receptor agonist CGS 21860 had no effect. In control preparations, inspiratory nerve activity and membrane potential fluctuations (29 of 35 cells) were not changed by adenosine, 2-chloro-N(6)-cyclopentyladenosine or CGS 21860. In the other six cells, adenosine evoked a hyperpolarization (<10 mV) with no major change in input resistance. The anticonvulsant effects of adenosine and 2-chloro-N(6)-cyclopentyladenosine were antagonized by the A(1) adenosine receptor blocker 8-cyclopentyl-1,3-dipropylxanthine. After pre-incubation with 8-cyclopentyl-1,3-dipropylxanthine, bicuculline also evoked seizure-like discharge in the hypoglossal nerve. The results indicate that seizure-like spinal motor output of the respiratory network upon block of Cl(-)-mediated inhibition is caused by disinhibition of spinal neuronal networks with afferent connections to the ventral respiratory group. Presynaptic A(1) adenosine receptors exert an anticonvulsant action on the disinhibited spinal motor network, but have no depressing effect per se on the isolated medullary respiratory network.

Adenosine↗