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PubMed1989

How visual inputs to the ponto-bulbar reticular formation are used in the synthesis of premotor signals during orienting.

The primate superior colliculus (SC) is known as a structure subserving the transformation of visual information into "commands" for orienting eye movements. Collicular burst neurons discharging with short lead times in relation to visually triggered or spontaneous saccades are supposed to be the output elements linking the SC to immediately premotor pattern generators. In this paper we summarize some data available for the cat's SC neurones, identified as tecto-reticulo-spinal projection cells (TRSN), and reticulospinal neurones (RSN), identified as receiving excitatory collicular input. Some TRSNs respond to visual stimuli in the absence of orienting movements and, hence, their signals cannot be regarded as motor "commands", in spite of their proven connections with premotor pools in the brain stem and with the spinal cord. Moreover, a small fraction of RSNs belonging to polysynaptic descending collicular pathways also displays visual responses dissociated from movement, in addition to discharges related to the performance of orienting eye-head synergies. The processes of visual to motor transformation, assumed by current models as being definitively accomplished in the SC, appear thus to be partially performed in the reticular network incorporating the overlapping collaterals of tectal projection cells and their target neurons in the reticular core. It is concluded that, at least as for visuomotor transformations underlying orienting movements in the cat, the deep division of the SC and the brain stem reticular formation represent an ensemble, rather than a sequence of hierarchically arranged levels of processing.

Action Potentials↗
PubMed1996

Dynamics of functional connectivity in visual cortical networks: an overview.

The aim of the Royaumont Symposium was to review various dynamic aspects of adaptive changes in functional connectivity, expressed in cortical networks during development, learning, and possibly during recognition and cognitive processing. The link between the various experimental and theoretical models was the comparison of cellular and molecular mechanisms that could be involved in the up- and down-regulation of functional connectivity, over different time scales. These processes have been investigated using several approaches in parallel: 1) at the molecular/subcellular level, to identify postsynaptic receptors (NMDA, mGluR) and second messengers (calcium protein kinases and phosphatases) involved in the induction of synaptic potentiation and depression, and to characterize diffusible factors (NO), released pre- or postsynaptically, involved in the spatial generalization of local changes to neighboring synapses; 2) at the level of integrating networks, to develop electrophysiological (single and multiple recording), pharmacological and optical imaging techniques in order to compare the dynamics of adaptive processes put into play during the natural development of cortical specificity and connectivity, versus those triggered during forced regimes of temporal correlations between pre- and post synaptic activities. Both in vitro and in vivo approaches have been combined in the primary visual cortex of the developing and adult vertebrate (rat, guinea-pig, ferret, cat and monkey). The various forms of 'slow' synaptic plasticity, demonstrated during epigenesis and selective phases of learning in the adult, can be compared with 'fast' forms of functional coupling (or synchronous firing) shown to develop during the time span required for perception and cognitive processing Phenomenology of the dynamics in functional connectivity and their relative dependence on temporal correlation in neuronal activity have been analyzed in each of these situations. Experimental results have been compared at different levels of neuronal integration (synapse, column map and cell assembly) in order to gain a better understanding of functional grouping within cortical networks.

Adaptation, Physiological↗
PubMed2002

Curvature of co-links uncovers hidden thematic layers in the World Wide Web.

Beyond the information stored in pages of the World Wide Web, novel types of "meta-information" are created when pages connect to each other. Such meta-information is a collective effect of independent agents writing and linking pages, hidden from the casual user. Accessing it and understanding the interrelation between connectivity and content in the World Wide Web is a challenging problem [Botafogo, R. A. & Shneiderman, B. (1991) in Proceedings of Hypertext (Assoc. Comput. Mach., New York), pp. 63-77 and Albert, R. & Barabási, A.-L. (2002) Rev. Mod. Phys. 74, 47-97]. We demonstrate here how thematic relationships can be located precisely by looking only at the graph of hyperlinks, gleaning content and context from the Web without having to read what is in the pages. We begin by noting that reciprocal links (co-links) between pages signal a mutual recognition of authors and then focus on triangles containing such links, because triangles indicate a transitive relation. The importance of triangles is quantified by the clustering coefficient [Watts, D. J. & Strogatz, S. H. (1999) Nature (London) 393, 440-442], which we interpret as a curvature [Bridson, M. R. & Haefliger, A. (1999) Metric Spaces of Non-Positive Curvature (Springer, Berlin)]. This curvature defines a World Wide Web landscape whose connected regions of high curvature characterize a common topic. We show experimentally that reciprocity and curvature, when combined, accurately capture this meta-information for a wide variety of topics. As an example of future directions we analyze the neural network of Caenorhabditis elegans, using the same methods.

Animals↗
PubMed2002

Inhibitory interactions between spiny projection neurons in the rat striatum.

The spiny projection neurons are by far the most numerous type of striatal neuron. In addition to being the principal projection neurons of the striatum, the spiny projection neurons also have an extensive network of local axon collaterals by which they make synaptic connections with other striatal projection neurons. However, up to now there has been no direct physiological evidence for functional inhibitory interactions between spiny projection neurons. Here we present new evidence that striatal projection neurons are interconnected by functional inhibitory synapses. To examine the physiological properties of unitary inhibitory postsynaptic potentials (IPSPs), dual intracellular recordings were made from pairs of spiny projection neurons in brain slices of adult rat striatum. Synaptic interactions were found in 9 of 45 pairs of neurons using averages of 200 traces that were triggered by a single presynaptic action potential. In all cases, synaptic interactions were unidirectional, and no bidirectional interactions were detected. Unitary IPSPs evoked by a single presynaptic action potential had a peak amplitude ranging from 157 to 319 microV in different connections (mean: 277 +/- 46 microV, n = 9). The percentage of failures of single action potentials to evoke a unitary IPSP was estimated and ranged from 9 to 63% (mean: 38 +/- 14%, n = 9). Unitary IPSPs were reversibly blocked by bicuculline (n = 4) and had a reversal potential of -62.4 +/- 0.7 mV (n = 5), consistent with GABA-mediated inhibition. The findings of the present study correlate very well with anatomical evidence for local synaptic connectivity between spiny projection neurons and suggest that lateral inhibition plays a significant role in the information processing operations of the striatum.

Animals↗
PubMed2005

Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system.

Nicotinic transmission in the enteric nervous system (ENS) is extensive, but the role of individual nicotinic acetylcholine receptor (nAChR) subtypes in the functional connectivity of its plexuses has been elusive. Using monoclonal antibodies (mAbs) against neuronal alpha3-, alpha4-, alpha3/alpha5-, beta2-, beta4- and alpha7-subunits, combined with radioimmunoassays and immunocytochemistry, we demonstrate that guinea-pig enteric ganglia contain all of these nAChR-subunits with the exception of alpha4, and so, differ from mammalian brain. This information alone, however, is insufficient to establish the functional role of the identified nAChR-subtypes within the enteric networks and, ultimately, their specific contributions to gastrointestinal physiology. We have used voltage-sensitive dyes and a high-speed CCD camera, in conjunction with specific antagonists to various nAChRs, to elucidate some of the distinct contributions of the individual subtypes to the behaviour of enteric networks. In the guinea-pig, the submucous plexus has the extraordinary advantage that it is virtually two-dimensional, permitting optical recording, with single cell resolution, of the electrical activity of all of its neurones. In this plexus, the block of alpha3beta2-, alpha3beta4- and/or alpha7-nAChRs always results in a decrease in the magnitude of the synaptic response. However, the magnitude of the fast excitatory post-synaptic potentials (epsps) evoked by electrical stimulation of a neighbouring ganglion varies from cell to cell, reflecting the differential expression of subunits already observed using mAbs, as well as the strengths of the activated synaptic inputs. At the same time, we observe that submucous neurones have a substantial mecamylamine (Mec)-insensitive (non-nicotinic) component to their fast epsps, which may point to the presence of purinergic or serotonergic fast epsps in this system. In the myenteric plexus, on the other hand, the antagonist-induced changes in the evoked synaptic response vary depending upon the location of the stimulating electrode with respect to the ganglion under study. The range of activity patterns that follows sequential pharmacological elimination of individual subtypes suggests that nAChRs may be capable of regulating the activity of both excitatory and inhibitory pathways, in a manner similar to that described in the central nervous system.

Animals↗
PubMed2002

Reflective self-awareness and conscious states: PET evidence for a common midline parietofrontal core.

A recent meta-analysis has shown precuneus, angular gyri, anterior cingulate gyri, and adjacent structures to be highly metabolically active in support of resting consciousness. We hypothesize that these regions constitute a functional network of reflective self-awareness thought to be a core function of consciousness. Seven normal volunteers were asked to think intensely on how they would describe the personality traits and physical appearance of themselves and a neutral reference person known to all the subjects (the Danish Queen). During each of the four conditions cerebral blood flow distribution was measured by the intravenous H(2)(15)O PET scanning technique. During scanning, no sensory or motor activity was intended. After each scan, the subjects reported the contents of their thoughts during the scan to ascertain that the instructions had been followed. The results confirmed our hypothesis: Statistical parametric mapping showed differential activity in precuneus and angular gyri during reflection on own personality traits and in anterior cingulate gyri during reflection on own physical traits. Connectivity analysis of synchrony showed these regions to be functionally connected during reflective self-awareness. The commonality between the neural networks of the resting conscious state and self-awareness reflects the phenomenological concept of a fundamental contribution of reflective self-awareness to the contents and coherence of the conscious state.

Adult↗
PubMed1982

Immunoreactive material resembling ovine prolactin in perikarya and nerve terminals of the rat hypothalamus.

The presence of prolactin (PRL)-like material is demonstrated in the brain of rats with the aid of anti-ovine PRL (oPRL) IgG as primary antibody in the unlabeled antibody-enzyme method. Immunoreactive deposits are visualized as an intraneuronal constituent with a widespread distribution in the hypothalamus and neural lobe of the pituitary. Dense networks of reactive nerve terminals derived from two prominent fibre tracts, a ventral (VHT) and a dorsal hypothalamo-neurohypophysial tract (DHT) are seen. The VHT is confined to the median eminence and pars oralis tuberis, the DHT to the pars caudalis tuberis. Both fibre tracts pass through the infundibular stalk into the neural lobe. The origin of the immunoreactive nerve terminals can be elucidated only to some extent. The VHT gives off beaded fibres entering the ependymal and glandular layer of the median eminence. Immunoreactive perikarya are observed in the supraoptic nucleus, the paraventricular nucleus, the anterior hypothalamic nucleus, the anterior commissural nucleus, the preoptic nucleus and the interstitial nucleus of the stria terminalis. A few of the immunoreactive perikarya are observed in close connection with brain vessels and the ependymal cells of the third ventricle. The results indicate that the anti-oPRL has a unique region specificity implying that only a segment of the mammalian PRL molecule is present in these nuclei of the brain. Fragments of PRL may function as neuromodulators or neurotransmitters in the rat brain.

Animals↗
PubMed2006

Connections of the subiculum of the rat: topography in relation to columnar and laminar organization.

This paper summarizes published as well as yet unpublished data on the organization of the subiculum. Because of the complex three-dimensional structure of the hippocampus, all traditional planes of sectioning will result in sections that at some point or another do not cut through the hippocampus at an angle that is perpendicular to its long axis; particular focus therefore is on data using the so-called extended preparation. On the basis of our yet fragmented insights in the intrinsic network, as well as the known organization of major efferents and afferents, we propose that the subiculum is organized as a matrix of columnar modules along the transverse axis showing partial laminar connectivity. Although many pieces of the large-scale puzzle on the subicular neuronal network as part of an input-output network for the hippocampus are still missing, it appears that subicular organization is different from that known for CA1. This indicates that major functional differences between CA1 and the subiculum are to be expected.

Animals↗
PubMed1997

Development of intrinsic connections in cat somatosensory cortex.

We explored the development of clustered connections in cat somatosensory cortex by using intracortical injections of biocytin and carbocyanine dye (DiI). Biocytin injections in adults revealed clusters of retrogradely labeled cells, affirming earlier reports of the patchy nature of corticocortical connectivity in the adult cat somatosensory cortex. On postnatal days (PNDs) 1 and 3, a diffuse distribution of axons and labeled cells were found after DiI injections. A dramatic rearrangement of connections had taken place by PND 6. Well-defined clusters of labeled cells surrounded the injection site. Intercluster zones were relatively free of labeled cells and contained few labeled axons. At later ages (PNDs 12 and 15), a clear patchy distribution of intrinsic connections was seen. We analyzed neuronal clustering by using spatial point process analysis, which corroborated our qualitative observations. The density of labeled neurons was significantly higher in clusters than in the intercluster zones on PND 6. Autocorrelations run on profile plots of optical density values, along paths parallel to the edge of the injection sites (reflecting axonal distributions), revealed significant periodicity (P < .05; center-to-center approximately 750 pm) by PND 6. These data demonstrate that corticocortical connections in cat somatosensory cortex develop from a diffuse network at birth, which transforms into a patchy network by the end of the 1st postnatal week. This is substantially earlier than the development of local circuits in the cat visual cortex and may reflect fundamental differences in the organization of the two cortices.

Animals↗
PubMed2003

Induced oscillations and the distributed cortical sources during the Wisconsin card sorting test performance in schizophrenic patients: new clues to neural connectivity.

Prefrontal dysfunction has been associated with schizophrenia. Activation during Wisconsin card sorting test (WCST) is a common approach used in functional neuroimaging to address this failure. Equally, current knowledge states that oscillations are basic forms of cells-assembly communications during mental activity. Promising results were revealed in a previous study assessing healthy subjects, WCST and oscillations. However, those previous studies failed to meet the functional integration of the network during the WCST in schizophrenics, based on the induced oscillations and their distributed cortical sources. In this research, we utilized the brain electrical tomography (variable-resolution brain electromagnetic tomography) technique to accomplish this goal. Task specific delta, theta, alpha and beta-2 oscillations were induced and simultaneously synchronized over large extensions of cortex, encompassing prefrontal, temporal and posterior regions as in healthy subjects. Every frequency had a well-defined network involving a variable number of areas and sharing some of them. Oscillations at 11.5, 5.0 and 30 Hz seem to reflect an abnormal increase or decrease, being located at supplementary motor area (SMA), left occipitotemporal region (OT), and right frontotemporal subregions (RFT), respectively. Three cortical areas appeared to be critical, that may lead to difficulties either in coordinating/sequencing the input/output of the prefrontal networks-SMA, and retention of information in memory-RFT, both preceded or paralleled by a deficient visual information processing-OT.

Adult↗
PubMed1987

Somatostatin 28 and neuropeptide Y innervation in the septal area and related cortical and subcortical structures of the human brain. Distribution, relationships and evidence for differential coexistence.

Somatostatin 28- and neuropeptide Y-containing innervations were mapped in the human medial forebrain (eight control brains) with immunohistochemistry, using the sensitive avidin-biotin-peroxidase method. Peptidergic perikarya and fibers had an extensive distribution: they were densest in the ventral striatum (nucleus accumbens, olfactory tubercle and bed nucleus of the stria terminalis) and infralimbic cortex, of intermediate density in the medial septal area and of lowest density in the dorsal and caudal lateral septal nucleus. Somatostatin-like immunoreactive perikarya and fibers were generally more numerous than the neuropeptide Y-like immunoreactive ones, but more faintly labeled. Their pattern of distribution was strikingly similar in some of the limbic structures studied but clearly distinct in others. Excellent overlap of neuropeptide Y and somatostatin-like immunoreactivity was detected in: (1) the medial septal area, where innervation occasionally formed perivascular clusters; (2) the nucleus accumbens and olfactory tubercle, characterized by dense patchy innervation; and (3) the laterodorsal septal nucleus, scarcely innervated. In the latter structures, most peptidergic neurons were double-labeled. On the other hand, both peptidergic innervations clearly differed in the lateroventral septal nucleus and the bed nucleus of the stria terminalis which contained distinct clusters of somatostatin-like immunoreactive neurons devoid of neuropeptide Y-like immunoreactivity. Also, the perineuronal and peridendritic axonal plexuses ('woolly fibers') present in these structures were only labeled with somatostatin. In the infralimbic cortex, the relation between the peptides varied according to the cortical laminae. Coexistence of somatostatin and neuropeptide Y frequently occurred in layer VI and in the subcortical white matter, whereas layer V and particularly layers II and III contained a contingent of neurons labeled only with somatostatin. Dense horizontal terminal networks in layers I and VI however were similar for both peptides. These findings support the existence of two different types of somatostatin-like immunoreactive perikarya as regards colocalization with neuropeptide Y. Their particular topographical segregation within the cortical and subcortical structures analysed suggest that they could have different connections and functional properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2001

On multivariate spectral analysis of fMRI time series.

Most of functional magnetic resonance imaging (fMRI) time series analysis is based on single voxel data evaluation using parametric statistical tests. The result of such an analysis is a statistical parametric map. Voxels with a high significance value in the parametric test are interpreted as activation regions stimulated by the experimental task. However, for the investigation of functional connectivities it would be interesting to get some detailed information about the temporal dynamics of the blood oxygen level-dependent (BOLD) signal. For investigating that behavior, a method for fMRI data analysis has been developed that is based on Wiener theory of spectral analysis for multivariate time series. Spectral parameters such as coherence measure and phase lead can be estimated. The resulting maps give detailed information on brain regions that belong to a network structure and also show the temporal behavior of the BOLD response function. This paper describes the method and presents a visual fMRI experiment as an example to demonstrate the results.

Adult↗
PubMed1977

Vascularization of the pars intermedia of the hypophysis in the toad, , Bufo bufo (L.) (Amphibia, Anura). A comparative light microscopical and scanning electron microscopical study. II.

The vascularization of the pars intermedia of the hypophysis of the toad, Bufo bufo (L.) was studied by injection of a mixture of India-ink and gelatine into the circulatory system of the head via the arteria carotis communis. Further methyl-methacrylate corrosion casts of brains were made and the hypophysial region of the corrosion casts was examined with the scanning electron microscope. The results showed that the vascularization of the pars intermedia of the toad hypophysis consists of a single-layered vascular network, which is located on the ventral surface of the pars intermedia. The network is formed by capillaries, which primarily run caudally in a fan-like manner and which show only a few cross-connections. In the rostral region of the pars intermedia this network lies rather superficially, while in the caudal region it slightly penetrates the parenchyma. The vascular network originates from vessels of the neural stalk and from wide capillaries of the rostro-ventral region of the neurointermediate junction. The venous drainage of the pars intermedia is exerted by veins, which leave the caudal region and drain into the veins leaving the venous pole of the pars distalis. The flat, wide meshed vascular net on the ventral side of the pars intermedia, demonstrated in this study, fits into the concept that the pars intermedia of the anuran hypophysis is under the control of nerve fibers coming from the hypothalamus.

Animals↗
PubMed1980

Isolation and partial characterization of a cage of filaments that surrounds the mammalian mitotic spindle.

Mitotic cells have been detergent extracted under conditions that support microtubule assembly. When HeLa cells are lysed in the presence of brain tubulin, mitotic-arrested cells nucleate large asters and true metaphase cells yield spindles that remain enclosed within a roughly spherical cage of filamentous material. Detergent-extracted mitotic Chinese hamster ovary (CHO) cells show a similar, insoluble cage but the mitotic apparatus is only occasionally stabilized. In later stages of mitosis, HeLa cages are observed in elongated and furrowed configurations. In the terminal stages of cell division, two daughter filamentous networks are connected by the intercellular bridge. When observed in the electron microscope the cages include fibers 7-11 nm in diameter. The polypeptide composition of cages isolated from mitotic HeLa cells is complex, but the major polypeptides are a group with mol wt ranging from 43,000-60,000 daltons and a high molecular weight polypeptide. CHO cells contain a subset of these proteins which includes a major 58,000-dalton and a high molecular weight polypeptide. Two different antisera directed against the vimentin-containing intermediate filaments bind to polypeptides in the electrophoretic profiles of isolated HeLa and CHO cages and stain the cages, as visualized by indirect immunofluorescence. These results suggest that the HeLa and CHO cages include intermediate filaments of the vimentin type. The polypeptide composition of HeLa cages suggests that they also contain tonofilaments. The cages apparently form as the cells enter mitosis. We propose that these filamentous cages maintain the structural continuity of the cytoplasm while the cell is in mitosis.

Animals↗
PubMed2025

Genetic variation influences food-sharing sociability in honey bees.

Individual variation in sociability is a central feature of every society. This includes honey bees, with some individuals well connected and sociable, and others at the periphery of their colony's social network. However, the genetic and molecular bases of sociability are poorly understood. Trophallaxis-a behavior involving sharing liquid with nutritional and signaling properties-comprises a social interaction and a proxy for sociability in honey bee colonies: more sociable bees engage in more trophallaxis. Here, we identify genetic and molecular mechanisms of trophallaxis-based sociability by combining genome sequencing, brain transcriptomics, and automated behavioral tracking. A genome-wide association study (GWAS) identified 18 single nucleotide polymorphisms (SNPs) associated with variation in sociability. Several SNPs were localized to genes previously associated with sociability in other species, including in the context of human autism, suggesting shared molecular mechanisms of sociability. Variation in sociability also was linked to differential brain gene expression, particularly genes associated with neural signaling and development. Using comparative genomic and transcriptomic approaches, we also detected evidence for divergent mechanisms underpinning sociability across species, including those related to reward sensitivity and encounter probability. These results highlight both potential evolutionary conservation of the molecular roots of sociability and points of divergence.

Animals↗
PubMed1990

Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study.

To evaluate microcirculatory disturbance and cerebral edema associated with subarachnoid hemorrhage (SAH), both stereological morphometry on the intraparenchymal capillary network and microgravimetry were performed on a rabbit SAH model. Autologous arterial blood (5 ml) was injected into the cisterna magna, and the animals were sacrificed at intervals of 6 hours, 1 day, 2 days, or 6 days after SAH. Capillaries in the piriform cortex, parasagittal cortex, and ventral brain stem of the midline-hemisectioned brain were injected with Evans blue dye 1 minute before sacrifice, and were planimetrically evaluated under a fluorescence microscope connected to an image analysis system. Stereological and morphological parameters including the volume density, surface density, numerical density, minimum intercapillary distance, and the diameter of Evans blue-perfused capillaries were also computed. In the piriform cortex and ventral brain stem, the volume and surface densities were significantly reduced and the minimum intercapillary distance was significantly increased 1 to 2 days after SAH. In the parasagittal cortex far from the cisternal clot, changes in the parameters were minimal. Cerebral blood volume (CBV) in the normal condition and edema formation associated with SAH were studied by the microgravimetric technique. The mean CBV in the parasagittal cortex, piriform cortex, and brain stem was 6.9%, 6.8%, and 5.6%, respectively. Following SAH, specific gravity in the piriform cortex and the ventral brain stem of the other side of the hemisectioned brain was significantly decreased at 1 to 2 days, showing a change parallel to that of the stereological parameters. The results obtained from the morphometric technique indicated the occurrence of impaired capillary perfusion and reduced capillary blood volume following SAH, while microgravimetry suggested the formation of brain edema during this period. These changes in the intraparenchymal vessels may play an important role in the pathophysiology of SAH.

Analysis of Variance↗
PubMed1999

Associative memory properties of multiple cortical modules.

The existence of recurrent collateral connections between pyramidal cells within a cortical area and, in addition, reciprocal connections between connected cortical areas, is well established. In this work we analyse the properties of a tri-modular architecture of this type in which two input modules have convergent connections to a third module (which in the brain might be the next module in cortical processing or a bi-modal area receiving connections from two different processing pathways). Memory retrieval is analysed in this system which has Hebb-like synaptic modifiability in the connections and attractor states. Local activity features are stored in the intra-modular connections while the associations between corresponding features in different modules present during training are stored in the inter-modular connections. The response of the network when tested with corresponding and contradictory stimuli to the two input pathways is studied in detail. The model is solved quantitatively using techniques of statistical physics. In one type of test, a sequence of stimuli is applied, with a delay between them. It is found that if the coupling between the modules is low a regime exists in which they retain the capability to retrieve any of their stored features independently of the features being retrieved by the other modules. Although independent in this sense, the modules still influence each other in this regime through persistent modulatory currents which are strong enough to initiate recall in the whole network when only a single module is stimulated, and to raise the mean firing rates of the neurons in the attractors if the features in the different modules are corresponding. Some of these mechanisms might be useful for the description of many phenomena observed in single neuron activity recorded during short term memory tasks such as delayed match-to-sample. It is also shown that with contradictory stimulation of the two input modules the model accounts for many of the phenomena observed in the McGurk effect, in which contradictory auditory and visual inputs can lead to misperception.

Action Potentials↗
PubMed2000

Blockade of neuronal activity during hippocampal development produces a chronic focal epilepsy in the rat.

During brain development, neuronal activity can transform neurons characterized by widely ranging axonal projections to ones with more restricted patterns of synaptic connectivity. Previous studies have shown that an exuberant outgrowth of local recurrent excitatory axons occurs in hippocampal area CA3 during postnatal weeks 2 and 3. Axons are remodeled with maturation, and nearly half of the branches are eliminated. Postnatal weeks 2 and 3 also coincide with a "critical" period of development, when CA3 networks have a marked propensity to generate electrographic seizures. In an attempt to prevent axonal remodeling, local circuit activity was blocked unilaterally in dorsal hippocampus by continuous infusion of tetrodotoxin (TTX). Field potential recordings from behaving animals were dramatically altered when TTX infusion was initiated at the beginning of the critical period, week 2, but not later in life. Spontaneous, synchronized spikes and electrographic seizures with behavioral accompaniments were observed after 4 weeks of TTX infusion and persisted into adulthood. When recordings were made during TTX infusion, synchronized spiking was recorded in ventral hippocampus as early as 2 weeks after infusate introduction. At this same time, extracellular field recordings from in vitro slices demonstrated spontaneous network-driven "mini-bursts" arising from ventral hippocampal slices. These were abolished by glutamate receptor antagonists. Whole-cell recordings from CA3 neurons revealed bursts of excitatory synaptic potentials coincident with the network bursts recorded extracellularly. Thus, local assemblies of mutually excitatory CA3 pyramidal cells are hyperexcitable in these rats. Whether alterations in developmental axonal remodeling mediate these effects awaits further studies.

Animals↗