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PubMed2002

Computational modeling of pair-association memory in inferior temporal cortex.

Distinctive neuronal activities related to visual stimulus-stimulus association have been found in the inferior temporal (IT) cortex of monkeys. They provide an important clue to elucidating the memory mechanisms of the brain, but do not accord with existing neural network models. In the present paper, we clarify the computational principle required for reproducing the empirical data and construct a biologically feasible model that learns and performs a delayed pair-association task. This model is composed of two neural networks, association network N1 and trainer network N2, and pair-association memories are formed by their interactions. Specifically, N2 receives the output of N1 in addition to an external input, and sends a learning signal back to N1; this signal works as a guide for shifts in output pattern or state transitions of N1, and memory traces are engraved along its path, so that a trajectory attractor connecting from the cue-coding to the target-coding state is formed in N1. Computer simulation shows that the model not only distinguishes the target in the task, but also explains the activity of the IT neurons very well. It is reasonable to presume that N1 and N2 correspond to area TE and the rhinal cortex, respectively; based on this theory, we explain some physiological findings on learning and memory, and also make several predictions.

Algorithms↗
PubMed1998

Targeted disruption of the GRA2 locus in Toxoplasma gondii decreases acute virulence in mice.

Following invasion into the host cell, the protozoan Toxoplasma gondii secretes a variety of proteins that modify the parasitophorous vacuole. Within the vacuole, the 28-kDa dense granule protein known as GRA2 is specifically targeted to the tubulovesicular network which forms connections with the vacuolar membrane. To investigate the importance of GRA2, we derived from strain RH a mutant T. gondii line in which GRA2 was disrupted by replacement with the marker Ble (selecting for phleomycin resistance). The Deltagra2 mutant invaded and grew normally in both fibroblasts and macrophages in vitro; however, it was less virulent during acute infection in mice. The survival rate of mice inoculated with Deltagra2 was significantly higher; some infected mice survived the acute infection, whereas all mice infected with the wild-type strain RH succumbed to early death. Chronic infection by Deltagra2 was detected by positive serology, immunohistochemical detection of parasites and cysts in the brain, and reisolation of parasites by bioassay at 6 weeks postinfection. Thus, absence of GRA2 partially attenuates the virulence of T. gondii during the acute phase of infection and allows for establishment of chronic infection by the otherwise highly virulent RH strain. These results establish that GRA2 plays an important role during in vivo infection and provide a potential model for examining acute pathogenesis by T. gondii.

Animals↗
PubMed1995

Psychotic disorder caused by a general medical condition, with delusions. Secondary "organic" delusional syndromes.

Many medical and neurologic disorders cause psychosis with delusions. The pathophysiology of this final common pathway may shed light on idiopathic psychotic disorders such as schizophrenia. By focusing on the "basal ganglia-thalamocortical" and "corticostriatal-thalamocortical" loops that connect limbically related cortical regions with the mesolimbic-mesostriatal dopamine system we can view the neural network that may produce delusional thinking when its restitutive function fails. Given its importance in the memory system of the medial temporal lobe, as the recipient of the emotional valencing from the amygdala, and as a key "loop" structure for cognitive functional integrity, the hippocampus may be a nodal area in the development of rational as opposed to delusional thinking.

Brain↗
PubMed1996

[Psychological stress and neuronal plasticity. An expanded model of the stress reaction process as the basis for understand central nervous system adaptation processes].

A short survey on results and theories in psychosomatic and neurobiologic stress research is presented. Based on a comprehensive definition of the stress-reaction process, the biological and psychological consequences are described which are elicited by either controllable or uncontrollable stress. We conclude that controllable stress triggers the stabilization and facilitation of neuronal networks involved in the generation of appropriate patterns of appraisal and coping, whereas uncontrollable stress favours the extinction of inappropriate patterns and the reorganisation of neuronal connections underlying certain inappropriate behaviors. Both, controllable an uncontrollable stress-reaction-processes are therefore essential prerequisites of, and inherent challenges to, the development and adaptation of an individual in an ever changing external world but may also lead to psychodevelopmental failures and psychosomatic diseases.

Adaptation, Psychological↗
PubMedDate not supplied

Background gamma-oscillations in neuronal networks with interhemisphere connections.

Results obtained in studies of the high-frequency components of EEG recordings and in modeling, determining the conditions for the appearance of gamma oscillations in interneuronal interactions, were compared with features of the background gamma oscillations recorded in the activity of interacting neurons located in symmetrical loci of the right and left hemisphere motor areas in anesthetized rats. Similarities in high frequencies extracted from EEG recordings and in the most commonly observed gamma oscillation frequencies suggested that these oscillations may represent one of the mechanisms underlying the high-frequency EEG component. Published modeling data indicating that the formation of these oscillations involves reciprocal inhibitory connections, along with our own data that interhemisphere oscillations are seen 1.5 times more commonly than ipsilateral oscillations, suggested that transcallosal inhibition is more effective than inhibition between neighboring cells. Simultaneously extracted background oscillations in the interacting activity of callosal cells and neighboring cells could be different, as could those characterizing the activity of individual neurons. It is suggested that these differences underlie the functional heterogeneity of local cortical neuronal networks and explain the fact that these networks contain various types of inhibitory neurons.

Animals↗
PubMed1994

Experimental neurobiology of epilepsies.

Epileptic discharges are a pathological extreme of neuronal synchrony. Experimental models of both focal and primary generalized epilepsies reveal the importance of the interaction of intrinsic (membrane current) properties of neurons and the synaptic networks which connect them. Focal epilepsies depend on excitatory networks within individual cortical structures, but full seizures may require widely dispersed neuronal networks. Absence seizures are generated by the thalamocortical system, and depend on inhibitory postsynaptic potentials, Ca2(+)-activated K+ currents and low threshold "T" currents. Other forms of synchronization can occur under particular circumstances, including field effects and gap junctions, but at the moment appear to be less generally involved in epileptogenesis. The cellular and network mechanisms of chronic experimental epilepsies are more complex and involve synaptic reorganization, and functional disconnection of inhibitory neurons.

Animals↗
PubMed1987

Ultrastructure of complex carbohydrates of rodent and monkey ependymal glycocalyx and meninges.

The surfaces of the brain offer metabolic and mechanical support to the underlying parenchyma. Mouse, rat, and monkey brains were fixed by immersion in a glutaraldehyde fixative or glutaraldehyde with cetylpyridinium chloride, followed by block staining for complex carbohydrates using alcian blue with OsO4 postfixation, or OsO4 postfixative solution containing ruthenium red, or alcian blue and then ruthenium red-OsO4 treatment. The ependyma in these species had a glycocalyx extending into the ventricular fluid as a finely filamentous network when stained with alcian blue or with alcian blue followed by ruthenium red-OsO4. Mice in the middle age range had stained material in this glycocalyx resembling the hyaluronic acid reported in the ocular vitreous body. Similar material was seen in the arachnoidal space of these mice and in the inner connective tissue matrix of the dura mater. Both the mouse and monkey had a cell-free zone, termed the inner dural matrix zone, between the thick fibrous dura and its innermost cellular layer. This zone contained filamentous and globular alcian blue-stained material. The complex carbohydrates of the mouse ependymal glycocalyx and inner dural matrix zone underwent changes developmentally. Aged rats were injected intraventricularly with latex beads, which, along with extravasated erythrocytes, were seen to adhere to the ependymal glycocalyx. A similar adhesion of erythrocytes was seen in the mouse and monkey ependymal glycocalyx and in the filamentous network of the mouse and monkey inner dural matrix zone. The ependymal glycocalyx, formed in part of complex carbohydrates, is much thicker than previously demonstrated. Some activities related to the ependymal lining of the ventricles, including the movement of cells or particles, the penetration of metabolites or serum-protein fractions (e.g., immunoglobulins), and cell-surface hydration, probably depend in part on complex carbohydrates that provide a sticky, electrically negative, hydrophilic environment. The complex carbohydrates in the inner dural matrix zone might provide mechanical buffering. Complex carbohydrates in the arachnoidal space may help to maintain a loose tissue that needs not only to be hydrated, but also to be open enough to provide cerebrospinal fluid circulation.

Animals↗
PubMed2005

Damage within a network of white matter regions underlies executive dysfunction in CADASIL.

OBJECTIVE: To identify the important sites of white matter disruption that underpin executive dysfunction in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a genetic model of pure subcortical vascular disease. METHODS: The anatomic pattern of correlation between tissue integrity and executive function was explored with diffusion tensor imaging (DTI), which provides quantitative measures of tissue integrity. Eighteen nondemented patients with CADASIL underwent DTI and cognitive assessment. DTI was normalized to a standard template and correlations assessed at every voxel across the brain with Statistical Parametric Mapping with cluster-level correction for multiple comparisons. RESULTS: For executive tasks, correlations were found in a number of discrete regions in the white matter of the frontal lobes. A distinct, nonoverlapping pattern of correlation was seen for verbal memory. Significant independent correlations remained in some regions after co-varying for age and IQ. CONCLUSIONS: Different cognitive functions correlate with structural integrity at different sites in the white and subcortical gray matter. The distribution of regions correlating specifically with executive function provides clues to the organization of the relevant cognitive networks and their important white matter projections. The cingulum bundle is one candidate tract that may carry anteroposterior connections important for executive processes.

Adult↗
PubMed1996

Inhibition of the respiratory pattern-generating neurons by an identified whole-body withdrawal interneuron of Lymnaea stagnalis

Respiration and the whole-body withdrawal are two incompatible behaviors in the freshwater snail Lymnaea stagnalis. Whole-body withdrawal behavior is believed to be higher on the behavioral hierarchy than respiratory behavior. A central pattern generator (CPG) underlies respiratory behavior; whole-body withdrawal is mediated by a network of electrically coupled neurons. In this study, we provide evidence that the behavioral hierarchy between the whole-body withdrawal and the respiratory behaviors is established at the interneuronal level. We demonstrate that an identified whole-body withdrawal interneuron inhibits both muscular and neuronal components of the respiratory behavior in Lymnaea stagnalis. A pair of identified, electrically coupled interneurons, termed left and right pedal dorsal 11 (L/RPeD11), coordinates the whole-body withdrawal behavior in Lymnaea stagnalis. In the present study, RPeD11 inhibited spontaneously occurring respiratory CPG activity in isolated brain preparations. In addition, electrical stimulation of RPeD11 in a semi-intact preparation also inhibited respiratory CPG interneuron RPeD1. The synaptic connections between RPeD11 and the respiratory CPG neurons RPeD1 and visceral dorsal 4 (VD4) persisted in the presence of high-Ca2+/high-Mg2+ saline, suggesting the possibility that they may be monosynaptic. In a semi-intact preparation (lung­mantle, pneumostome and central nervous system), electrical stimulation of RPeD11 induced pneumostome and columellar muscle contractions while inhibiting the activity of RPeD1. Moreover, mechanical stimulation of the respiratory orifice, the pneumostome, excited RPeD11, while its effects on the respiratory CPG neuron (RPeD1) were inhibitory. To determine the monosynaptic nature of connections between RPeD11 and the respiratory CPG neurons in the intact nervous system, we constructed these synapses in culture. RPeD11 and individual respiratory interneurons were isolated from their respective ganglia and co-cultured under conditions that support neurite outgrowth. Following neuritic overlap, RPeD11 was found to establish inhibitory synapses with the respiratory interneurons, supporting the hypothesis that these synaptic connections are likely to be monosynaptic in the intact central nervous system.

Journal Article↗
PubMedDate not supplied

Identification of central nervous system neurons innervating the respiratory muscles of the mouse: a transneuronal tracing study.

In recent years, the central control of breathing in mammals has been the subject of numerous studies. The aim of the present one was to characterize the neuronal network projecting to the main respiratory motoneurons, in adult mice. To this end, the morphology and location of the respiratory motoneurons and their sequential connections with other neurons were revealed using a transneuronal tracing technique by means of the rabies virus infection. The injections of the rabies virus in the respiratory muscles resulted in labeling the motoneurons and their serially connected interneurons at multiple levels of the mouse central nervous system: spinal cord, pons and medulla, cerebellum, mesencephalon, diencephalon, and telencephalon. Most of these labeled areas have been previously identified in the control of cardiorespiratory regulation, as well as in other autonomic functions. These anatomical data provide support for the integration of respiratory-related activities in complex behavioral responses. Furthermore, these data suggest similarities in the evolution of central respiratory networks in mammals.

Animals↗
PubMed2000

Interhemispheric asymmetries of the modular structure in human temporal cortex.

Language-relevant processing of auditory signals is lateralized and involves the posterior part of Brodmann area 22. We found that the functional lateralization in this area was accompanied by interhemispheric differences in the organization of the intrinsic microcircuitry. Neuronal tract tracing revealed a modular network of long-range intrinsic connections linking regularly spaced clusters of neurons. Although the cluster diameter was similar in both hemispheres, their spacing was about 20 percent larger in the left hemisphere. Assuming similar relations between functional and anatomical architecture as in visual cortex, the present data suggest that more functionally distinct columnar systems are included per surface unit in the left than in the right area 22.

Adult↗
PubMed2003

Dynamic causal modelling.

In this paper we present an approach to the identification of nonlinear input-state-output systems. By using a bilinear approximation to the dynamics of interactions among states, the parameters of the implicit causal model reduce to three sets. These comprise (1) parameters that mediate the influence of extrinsic inputs on the states, (2) parameters that mediate intrinsic coupling among the states, and (3) [bilinear] parameters that allow the inputs to modulate that coupling. Identification proceeds in a Bayesian framework given known, deterministic inputs and the observed responses of the system. We developed this approach for the analysis of effective connectivity using experimentally designed inputs and fMRI responses. In this context, the coupling parameters correspond to effective connectivity and the bilinear parameters reflect the changes in connectivity induced by inputs. The ensuing framework allows one to characterise fMRI experiments, conceptually, as an experimental manipulation of integration among brain regions (by contextual or trial-free inputs, like time or attentional set) that is revealed using evoked responses (to perturbations or trial-bound inputs, like stimuli). As with previous analyses of effective connectivity, the focus is on experimentally induced changes in coupling (cf., psychophysiologic interactions). However, unlike previous approaches in neuroimaging, the causal model ascribes responses to designed deterministic inputs, as opposed to treating inputs as unknown and stochastic.

Arousal↗
PubMed2005

Stochastic resonance of localized activity driven by common noise.

We study the influence of spatially correlated noise on the transient dynamics of a recurrent network with Mexican-Hat-type connectivity. We derive the closed form of the order parameter functional in the thermodynamical limit of neuron number N. Our analysis shows that network dynamics is qualitatively changed by the presence of common noise. Network dynamics driven by common noise obtains the global level of fluctuation, which is not observed in a network driven by independent noise only. We show that the optimal level of global fluctuation enhances the transition from non-localized firing states to spatially localized firing states, and also enhances the rotation speed of localized activity.

Brain↗
PubMed2006

LONI visualization environment.

Over the past decade, the use of informatics to solve complex neuroscientific problems has increased dramatically. Many of these research endeavors involve examining large amounts of imaging, behavioral, genetic, neurobiological, and neuropsychiatric data. Superimposing, processing, visualizing, or interpreting such a complex cohort of datasets frequently becomes a challenge. We developed a new software environment that allows investigators to integrate multimodal imaging data, hierarchical brain ontology systems, on-line genetic and phylogenic databases, and 3D virtual data reconstruction models. The Laboratory of Neuro Imaging visualization environment (LONI Viz) consists of the following components: a sectional viewer for imaging data, an interactive 3D display for surface and volume rendering of imaging data, a brain ontology viewer, and an external database query system. The synchronization of all components according to stereotaxic coordinates, region name, hierarchical ontology, and genetic labels is achieved via a comprehensive BrainMapper functionality, which directly maps between position, structure name, database, and functional connectivity information. This environment is freely available, portable, and extensible, and may prove very useful for neurobiologists, neurogenetisists, brain mappers, and for other clinical, pedagogical, and research endeavors.

Brain Mapping↗
PubMed1987

Colocalization of microtubule-associated protein 1A and microtubule-associated protein 2 on neuronal microtubules in situ revealed with double-label immunoelectron microscopy.

Microtubule-associated protein 1A (MAP1A) and microtubule-associated protein 2 (MAP2) were shown to be colocalized on the same microtubules (MTs) within neuronal cytoskeletons by double-label immunoelectron microscopy. To investigate the electron microscopic disposition of MAP1A and MAP2 and their relationship to MTs in vivo, and to determine whether there are different subsets of MTs which specifically bind either MAP1 or MAP2, we employed a double-label immunogold procedure on rat cerebella using mouse monoclonal antibody against rat brain MAP1A and affinity-purified rabbit polyclonal antibody against rat brain MAP2. MAP1A and MAP2 were identified with secondary antibodies coupled to 10- and 5-nm gold particles, respectively. In Purkinje cell dendrites, both 10- and 5-nm gold particles were observed to be studded on the fuzzy structures attached to the same MTs. Many such structures connected MTs to each other. There was no particular MT which bound either MAP1A or MAP2 alone. Furthermore, there seemed to be no specific regions on MTs where either MAP1A or MAP2 was specifically attached. Hence, we conclude that MAP1A and MAP2 are colocalized on MTs in dendrites and assume that MAP1A and MAP2 have some interrelationship in vivo and that their interactions are responsible for forming the network of cross-bridges between MTs and MTs in neuronal cytoskeletons.

Animals↗
PubMedDate not supplied

[The problems of evaluating the automatized and exploratory intellectual actions of man].

On the basis of psychological testing two groups of subjects have been formed: "automatizators" and "searchers". The incompatibility in the individual structure of the ability to automatized and searching actions, according to the data, are connected with the presence of the complex of alternative signs of cognitive styles. The neurophysiological organization of searching and automatized intellectual actions was studied by a method of computer toposcopy of the synchronous electrical processes. It has been shown that there are spatial-frequency interactions of electrical processes of the cerebral cortex, characteristic for each of the two above mentioned individuals groups, which are probably based on the functioning of neuronal networks with different lability levels.

Adult↗
PubMed1987

Plasticity in the organization of adult cerebral cortical maps: a computer simulation based on neuronal group selection.

Recent experimental evidence from the somatosensory, auditory, and visual systems documents the existence of functional plasticity in topographic map organization in adult animals. This evidence suggests that an ongoing competitive organizing process controls the locations of map borders and the receptive field properties of neurons. A computer model based on the process of neuronal group selection has been constructed that accounts for reported results on map plasticity in somatosensory cortex. The simulations construct a network of locally connected excitatory and inhibitory cells that receives topographic projections from 2 receptor sheets corresponding to the glabrous and dorsal surfaces of the hand (a typical simulation involves approximately 1500 cells, 70,000 intrinsic and 100,000 extrinsic connections). Both intrinsic and extrinsic connections undergo activity-dependent modifications according to a synaptic rule based on heterosynaptic interactions. Repeated stimulation of the receptor sheet resulted in the formation of neuronal groups-local sets of strongly interconnected neurons in the network. Cells in most groups were found to have similar receptive fields: they were exclusively glabrous or dorsal despite equal numbers of anatomical connections from both surfaces. The sharpness of map borders was due to the sharpness of the underlying group structure; shifts in the locations of these borders resulted from competition between groups. Following perturbations of the input, the network underwent changes similar to those observed experimentally in monkey somatosensory cortex. Repeated local tapping on the receptor sheet resulted in a large increase in the magnification factor of the stimulated region. Transection of the connections from a glabrous region resulted in the organization of a new representation of corresponding dorsal region. The detailed simulations provide several insights into the mechanisms of such changes, as well as a series of predictions about cortical behavior for further experimental test.

Brain Mapping↗
PubMed1999

Analysis of functional magnetic resonance imaging data using self-organizing mapping with spatial connectivity.

Commonly used methods in analyzing functional magnetic resonance imaging (fMRI) data, such as the Student's t-test and cross-correlation analysis, are model-based approaches. Although these methods are easy to implement and are effective in analyzing data obtained with simple paradigms, they are not applicable in situations in which patterns of neuronal response are complicated and when fMRI response is unknown. In this work, Kohonen's self-organizing mapping (SOM), which is a model-free approach, is adapted for analyzing fMRI data. Because spatial connectivity is an important function in the identification of activation sites in functional brain imaging, it is incorporated into the SOM algorithm. Receiver operating characteristic analysis on simulated data shows that the new algorithm achieves measurable improvement over the standard algorithm. The applicability of the new algorithm is demonstrated on experimental data.

Algorithms↗