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PubMedDate not supplied

A morphologic study of the vasculature of malignant gliomas using thick celloidin sections and alkaline phosphatase stain.

The combination of 100 microm thick celloidin sections and alkaline phosphatase (AP) enzyme histochemistry of the vascular endothelium offers a greatly enhanced, 3D morphologic perspective and reveals intricate details of the vasculature of brain. A study of tumor specimens obtained at craniotomy from 6 patients with glioblastomas, 1 with anaplastic oligodendroglioma and 1 with juvenile pilocytic astrocytoma was undertaken using this technique. Five of the 6 glioblastomas, the anaplastic oligodendroglioma and the low-grade astrocytoma specimen showed uniform staining of afferent tumor blood vessels. In the glioblastomas, newly formed vessels formed dense, festooned networks at the advancing edges of the tumor. Feeding arteries entered the tumor at the junction between the edge of the tumor and adjacent brain or meninges and proceeded to form striking, coiled vessels and smaller branches. The density of both small arteries and veins was greatly increased within the tumor although there was much variability. Disordered arborization, arteriole to venous and arteriole to arteriole shunts were observed, leading to a situation where arteries connected directly to veins. In necrotic areas, there were often no AP-stained vessels. In many places, arterioles and capillaries were lacking. Numerous AP-negative veins of various sizes drained the tumors. Glomeruloid proliferations were presumptively identified as focal stain smudges or clusters of capillaries arising from nearby vascular channels. Increased alkaline phosphatase staining and/or focal new vessels were seen outside necrotic areas. The pilocytic astrocytoma and the oligodendroglioma showed less dense vascularity and no formation of the focal festoons of vessels shown by the glioblastomas. This technique may be useful for the study of tumor angiogenesis and to evaluate vascularity in experimental and human brain tumors after various therapies.

Adult↗
PubMed2003

The associative striatum: cortical and thalamic projections to the dorsocentral striatum in rats.

Corticostriatal projections to the dorsocentral striatum (DCS) were investigated using retrograde fluorescent axonal tracing. The DCS is of interest because of its role in directed attention and recovery from multimodal hemispatial neglect following cortical lesions of medial agranular cortex (AGm), an association area that is its major source of cortical input. A key finding was that the multimodal posterior parietal cortex (PPC) also contributes substantial input to DCS. This is significant because PPC and AGm are linked by corticocortical connections and are both critical components of the circuitry involved in spatial processing and directed attention. Other cortical areas providing input to DCS include visual association areas, lateral agranular cortex and orbital cortex. These areas also have reciprocal connections with AGm and PPC. Less consistent labeling was seen in somatic sensorimotor areas FL, HL and Par 1. Thalamic afferents to DCS are prominent from the intralaminar, ventrolateral, mediodorsal, ventromedial, laterodorsal (LD) and lateral posterior (LP) nuclei. Collectively, these nuclei constitute the sources of thalamic input to cortical areas AGm and PPC. Nuclei LD and LP are only labeled with injections in dorsal DCS, the site of major input from PPC, and PPC receives its thalamic input from LD and LP. We conclude that DCS receives inputs from cortical and thalamic areas that are themselves linked by corticocortical and thalamocortical connections. These findings support the hypothesis that DCS is a key component of an associative network of cortical, striatal and thalamic regions involved in multimodal processing and directed attention.

Amidines↗
PubMed2005

Exploring the impact of plasticity-related recovery after brain damage in a connectionist model of single-word reading.

The effect of retraining a damaged connectionist model of single-word reading was investigated with the aim of establishing whether plasticity-related changes occurring during the recovery process can contribute to our understanding of the pattern of dissociations found in brain-damaged patients. In particular, we sought to reproduce the strong frequency x consistency interactions found in surface dyslexia. A replication of Plaut, McClelland, Seidenberg, and Patterson's (1996) model of word reading was damaged and then retrained, using a standard backpropagation algorithm. Immediately after damage, there was only a small frequency x consistency interaction. Retraining the damaged model crystallized out these small differences into a strong dissociation, very similar to the pattern found in surface dyslexic patients. What is more, the percentage of regularization errors, always high in surface dyslexics, increased greatly over the retraining period, moving from under 10% to over 80% in some simulations. These results suggest that the performance patterns of brain-damaged patients can owe as much to the substantial changes in the pattern of connectivity occurring during recovery as to the original premorbid structure. This finding is discussed in relation to the traditional cognitive neuropsychological assumptions of subtractivity and transparency.

Algorithms↗
PubMed2004

The functional anatomy of inspection time: an event-related fMRI study.

Twenty healthy young adults underwent functional magnetic resonance imaging (fMRI) of the brain while performing a visual inspection time task. Inspection time is a forced-choice, two-alternative visual backward-masking task in which the subject is briefly shown two parallel vertical lines of markedly different lengths and must decide which is longer. As stimulus duration decreases, performance declines to chance levels. Individual differences in inspection time correlate with higher cognitive functions. An event-related design was used. The hemodynamic (blood oxygenation level-dependent; BOLD) response was computed as both a function of the eight levels of stimulus duration, from 6 ms (where performance is almost at chance) to 150 ms (where performance is nearly perfect), and a function of the behavioral responses. Random effects analysis showed that the difficulty of the visual discrimination was related to bilateral activation in the inferior fronto-opercular cortex, superior/medial frontal gyrus, and anterior cingulate gyrus, and bilateral deactivation in the posterior cingulate gyrus and precuneus. Examination of the time courses of BOLD responses showed that activation was related specifically to the more difficult, briefer stimuli and that deactivation was found across most stimulus levels. Functional connectivity suggested the existence of two networks. One comprised the fronto-opercular area, intrasylvian area, medial frontal gyrus, and the anterior cingulate cortex (ACC), possibly associated with processing of visually degraded percepts. A posterior network of sensory-related and associative regions might subserve processing of a visual discrimination task that has high processing demands and combines several fundamental cognitive domains. fMRI can thus reveal information about the neural correlates of mental events which occur over very short durations.

Adult↗
PubMed1998

[Robotics in neurosurgery: current status and future prospects].

Neurosurgery is in essence a field of application development for robots, based on multimodal image guidance. Specific motorized tools have already been developed and routinely applied in stereotaxy to position a probe holder or in conventional neurosurgery to hold a microscope oriented towards a given target. The potentialities of these approaches have triggered industrial developments which are now commercially available. These systems use databases, primarily coming from multimodal numerical images from X-ray radiology to magnetic resonance imaging. These spatially encoded data are transferred through digital networks to workstations where images can be processed and surgical procedures are pre-planned, then transferred to the robotic systems to which they are connected. We have been using a stereotaxic robot since 1989 and a microscope robot since 1995 in various surgical routine procedures. The future of these applications rely mainly on the technical progress in informatics, about image recognition to adapt the pre-planning to the actual surgical situation, to correct brain shifts (for instance), about image fusion, integrated knowledge such as brain atlases, as well as virtual reality. The future developments, covering surgical procedure, research and teaching, are sure to be far beyond our wildest expectations.

Forecasting↗
PubMed1993

The organization of neural systems in the primate cerebral cortex.

The primate cerebral cortex is a sheet composed of many distinct areas. Each of these areas receives a large number of afferent inputs from other cortical areas (and elsewhere) and in return issues a large number of output projections. The cortex is thus innervated by a very large number of cortico-cortical connections, so that the areas and their interconnections form a network of startling complexity. The complexity of this network presents a formidable topological problem that hinders understanding of its organization. Recently, however, an optimization analysis has been applied to the connections between visual cortical areas. This optimization analysis derived a structure for the cortical visual system, a system whose organization has been extensively explored, that is consistent with known organizational features. This paper concerns an application of the same approach to the cortico-cortical connections of other major sensory systems in the primate brain, and to the connections of the entire cerebral cortex, whose organizations have not been extensively explored. The latter analysis suggests the gross topological organization of the cortical information processing system of this animal, and shows the 'place' of individual areas within this organization. The results may be suggestive for further theory and experiment.

Animals↗
PubMed2003

What determines the frequency of fast network oscillations with irregular neural discharges? I. Synaptic dynamics and excitation-inhibition balance.

When the local field potential of a cortical network displays coherent fast oscillations ( approximately 40-Hz gamma or approximately 200-Hz sharp-wave ripples), the spike trains of constituent neurons are typically irregular and sparse. The dichotomy between rhythmic local field and stochastic spike trains presents a challenge to the theory of brain rhythms in the framework of coupled oscillators. Previous studies have shown that when noise is large and recurrent inhibition is strong, a coherent network rhythm can be generated while single neurons fire intermittently at low rates compared to the frequency of the oscillation. However, these studies used too simplified synaptic kinetics to allow quantitative predictions of the population rhythmic frequency. Here we show how to derive quantitatively the coherent oscillation frequency for a randomly connected network of leaky integrate-and-fire neurons with realistic synaptic parameters. In a noise-dominated interneuronal network, the oscillation frequency depends much more on the shortest synaptic time constants (delay and rise time) than on the longer synaptic decay time, and approximately 200-Hz frequency can be realized with synaptic time constants taken from slice data. In a network composed of both interneurons and excitatory cells, the rhythmogenesis is a compromise between two scenarios: the fast purely interneuronal mechanism, and the slower feedback mechanism (relying on the excitatory-inhibitory loop). The properties of the rhythm are determined essentially by the ratio of time scales of excitatory and inhibitory currents and by the balance between the mean recurrent excitation and inhibition. Faster excitation than inhibition, or a higher excitation/inhibition ratio, favors the feedback loop and a much slower oscillation (typically in the gamma range).

Action Potentials↗
PubMed1983

Interaction between vascular endothelial cells and vascular intimal spindle-shaped cells in vitro.

The interactions between human or bovine vascular endothelial cells and fibroblast-like vascular intimal spindle-shaped cells have been studied in vitro, using species-specific antibodies to identify the different components in mixed cultures. Pure cultures of endothelial cells grow as uniform, nonoverlapping monolayers, but this growth pattern is lost after the addition of spindle cells, probably because the extracellular matrix secreted by the latter causes the endothelial cells to modify the way they are attached to the substrate. The result is a network of tubular aggregates of endothelial cells in a three-dimensional 'polylayer' of spindle-shaped cells. On the other hand, endothelial cells added to growth-inhibited cultures of spindle-shaped cells will grow in sheets over the surface of the culture. Human endothelial cells grown in contact with spindle-shaped cells have a reduced requirement for a brain-derived endothelial growth factor. The interactions of endothelial cells and other connective tissue cells in vitro may be relevant to the mechanisms of endothelial growth and blood vessel formation in vivo, and emphasize the potential importance of extracellular matrix in controlling endothelial cell behaviour.

Animals↗
PubMed1994

The use of periodic acid-thiocarbohydrazide-silver protein-physical development (PA-TCH-SP-PD) procedure for the histochemical detection of neutral carbohydrates in the circumventricular organs of the rat.

A periodic acid-thiocarbohydrazide-silver protein-physical development (PA-TCH-SP-PD) procedure was applied to the rat circumventricular organs (CVOs), which are known to be specialized structures in the brain. In the rat CVOs, vivid PA-TCH-SP-PD reactions were obtained in the apical surface and cytoplasm of the ependymal cells of the subcommissural organ (SCO) and the epithelial cells in the choroid plexuses (CPs) examined, and similar positive reactions were detected in the vascular walls and perivascular connective tissues in all the CVOs tested. Further, varying intensities of PA-TCH-SP-PD reactions were noted in the neuronal and glial networks of the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO) and area postrema (AP). The results obtained in the present study indicate that in the rat CVOs the histologic structures mentioned contain varying amounts of neutral carbohydrates and possible histophysiological significances of these carbohydrates in these organs have been discussed with references to their functions.

Animals↗
PubMed2006

Magnetoencephalography and diffusion tensor imaging in gelastic seizures secondary to a cingulate gyrus lesion.

Gelastic seizures are relatively uncommon and rarely observed secondary to frontal lobe lesions. This report presents magnetoencephalography (MEG) and diffusion tensor imaging (DTI) findings in an adolescent with gelastic seizures secondary to a left anterior cingulate gyrus lesion. Ictal scalp video EEG showed bilateral frontal 4 Hz theta discharges. Interictal EEG showed left fronto-temporal spikes or sharp waves. Interictal MEG showed spike sources over bilateral temporal regions. DTI and tractography delineated slightly shifted corpus callosum posterior to the lesion, unaffected uncinate and inferior longitudinal fasciculi. The patient became seizure free for 12 months after surgical excision of a pleomorphic xanthoastrocytoma in the left anterior cingulate region. In our patient, MEG and EEG did not localize the deep-seated epileptogenic zone. The combination of DTI and neurophysiologic studies, however, possibly disclosed neuronal connections within the epileptic network and indicated that epileptic discharges propagated via the uncinate fibers from the primary epileptogenic zone in the anterior cingulate region to the mesial temporal region in this case with gelastic seizures secondary to a cingulate lesion.

Adolescent↗
PubMed2003

Hemispheric asymmetries in cerebral cortical networks.

Since the middle of the 19th century it has been recognized that several higher cognitive functions, including language, are lateralized in cerebral cortex. Neuropsychological studies on patients with brain lesions and rapid developments in brain imaging techniques have provided us with an increasing body of data on the functional aspects of language lateralization, but little is known about the substrate on which these specializations are realized. Much attention has been focused on the gross size and shape of cortical regions involved, but recent findings indicate that the columnar and connectional structure within auditory and language cortex in the left hemisphere are distinct from those in homotopic regions in the right hemisphere. These findings concern parameters that are closely linked to the processing architecture within the respective regions. Thus, the comparison of these microanatomical specializations with their respective functional counterparts provides important insights into the functional role of cerebral cortical organization and its consequences for processing of cortical information in the implementation of complex cognitive functions.

Acoustic Stimulation↗
PubMed1998

Interhemispheric communication is via direct connections.

Two priming experiments, using normal university students as subjects, independently projected low imagery primes and concrete target words to the left or right visual fields (LVF or RVF) to examine the merits of three spreading activation models of interhemispheric communication: (i) callosal relay of a semantically encoded prime; (ii) transfer of products activated as a result of the spread of activation; and (iii) direct connections between the hemispheres. The first experiment temporally separated pairs by a stimulus onset asynchrony (SOA) of 250 ms and obtained strong support for the direct connections model. Priming effects were obtained only when the prime was projected to the RVF and the target to the LVF. The pattern of priming effects suggested that low imagery words projected to the left hemisphere can activate concrete associates in the right hemisphere via direct callosal connections between the two. In the second experiment, the SOA was increased to 450 ms. This time, RVF-RVF priming was obtained along with RVF-LVF priming. The findings are interpreted within a modification of Bleasdale's (1987) framework, where abstract/low imagery words and concrete/high imagery words are represented in separate subsystems in the left hemisphere lexicon. Support was also found for the view that the left hemisphere is comprised of a complex network of abstract and concrete words, while the right hemisphere operates as a subsidiary word processor, subserving linguistic processing with a limited, special purpose lexicon comprised of associative connections between concrete, imageable words (e.g., Zaidel, 1983a; Bradshaw, 1980). Interhemispheric communication in the priming procedure appears to occur at the semantic level, via direct connections between the hemispheres.

Adult↗
PubMed1998

MuSC, a novel member of the immunoglobulin superfamily, is expressed in neurons of a subset of cranial sensory ganglia in the mouse embryo.

In contrast to the spinal sensory ganglia which reiterate a basic organizational and functional unit, each cranial ganglion mediates a distinct sensory modality and exhibits a characteristic pattern of peripheral and central neuronal connectivity. Molecules responsible for establishment and maintenance of the cranial ganglion-specific networks are not known. Our hamster monoclonal antibody 802C11 strongly stained neurons and their processes of the VIIIth cranial ganglion (hearing and equilibrium), but not of the Vth cranial (somatosensory) or spinal ganglia in the mouse embryo. The cellular staining pattern of positive neurons suggested that the antigen was associated with the cell membrane, and biochemical analyses of the antigen from adult mouse brain showed the antigen to be a glycosylated intrinsic membrane protein of approximately 100 kDa. The antigen was purified, and based on the partial amino acid sequences, its entire cDNA was cloned. A bacterially expressed polypeptide encoded by the cDNA was recognized by the antibody. The deduced amino acid sequence revealed that the antigen belongs to the immunoglobulin superfamily with a significant homology (73.5% identity) to chicken SC1 protein. Chicken SC1 has been shown to be a cell-cell adhesion molecule in vitro with a proposed role in neurite extension of spinal motor neurons. These results suggest that our murine SC1-related protein (MuSC) is involved in the pathfinding and/or fasciculation of specific cranial sensory nerve fibres.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2003

Memory processing during human sleep as assessed by functional neuroimaging.

Sleep is believed to participate in memory consolidation, possibly through off-line processing of recent memory traces. In this paper, we summarize functional neuroimaging data testing this hypothesis. First, sleep deprivation disrupts the processing of recent memory traces and hampers the changes in functional segregation and connectivity which underpin the gain in performance usually observed in subjects allowed to sleep on the first post-training night. Second, experience-dependent changes in regional brain activity occur during post-training sleep. These changes are shown to be related to the processing of high-level material and to be modulated by the amount of learning achieved during the training session. These changes do not involve isolated brain areas but entire macroscopic cerebral networks. These data suggest a role for sleep in the processing of recent memory traces.

Adult↗
PubMed2005

A review of systems and networks of the limbic forebrain/limbic midbrain.

Evolutionarily older brain systems, such as the limbic system, appear to serve fundamental aspects of emotional processing and provide relevant and motivational information for phylogenetically more recent brain systems to regulate complex behaviors. Overall, overt behavior is, in part, determined by the interactions of multiple learning and memory systems, some seemingly complementary and some actually competitive. An understanding of limbic system function in emotion and motivation requires that these subsystems be recognized and characterized as extended components of a distributed limbic network. Behavioral neuroscientists face the challenge of teasing apart the contributions of multiple overlapping neuronal systems in order to begin to elucidate the neural mechanisms of the limbic system and their contributions to behavior. One major consideration is to bring together conceptually the functions of individual components of the limbic forebrain and the related limbic midbrain systems. For example, in the rat the heterogeneous regions of the prefrontal cortex (e.g., prelimbic, anterior cingulate, subgenual cortices and orbito-frontal areas) make distinct contributions to emotional and motivational influences on behavior and each needs consideration in its own right. Major interacting structures of the limbic system include the prefrontal cortex, cingulate cortex, amygdaloid nuclear complex, limbic thalamus, hippocampal formation, nucleus accumbens (limbic striatum), anterior hypothalamus, ventral tegmental area and midbrain raphe nuclei; the latter comprising largely serotonergic components of the limbic midbrain system projecting to the forebrain. The posterior limbic midbrain complex comprising the stria medullaris, central gray and dorsal and ventral nuclei of Gudden are also key elements in the limbic midbrain. Some of these formations will be discussed in terms of the neurochemical connectivity between them. We put forward a systems approach in order to build a network model of the limbic forebrain/limbic midbrain system, and the interactions of its major components. In this regard, it is important to keep in mind that the limbic system is both an anatomical entity as well as a physiological concept. We have considered this issue in detail in the introduction to this review. The components of these systems have usually been considered as functional units or 'centers' rather than being components of a larger, interacting, and distributed functional system. In that context, we are oriented toward considerations of distributed neural systems themselves as functional entities in the brain.

Animals↗
PubMed2003

Fractones and other basal laminae in the hypothalamus.

The physiological role of basal laminae (BL) and connective tissue (meninges and their projections) in the adult brain is unknown. We recently described novel forms of BL, termed fractones, in the most neurogenic zone of the adult brain, the subependymal layer (SEL) of the lateral ventricle. Here, we investigated the organization of BL throughout the hypothalamus, using confocal and electron microscopy. New types of BL were identified. First, fractones, similar to those found in the lateral ventricle wall, were regularly arranged along the walls of the third ventricle. Fractones consisted of labyrinthine BL projecting from SEL blood vessels to terminate immediately beneath the ependyma. Numerous processes of astrocytes and of microglial cells directly contacted fractones. Second, another form of BL projection, termed anastomotic BL, was found between capillaries in dense capillary beds. The anastomotic BL enclosed extraparenchymal cells that networked with the perivascular cells coursing in the sheaths of adjacent blood vessels. Vimentin immunoreactivity was often detected in the anastomotic BL. In addition, the anastomotic BL overlying macrophages contained numerous fibrils of collagen. We also found that the BL located at the pial surface formed labyrinthine tube-like structures enclosing numerous fibroblast and astrocyte endfeet, with pouches of collagen fibrils at the interface between the two cell types. We suggest that cytokines and growth factors produced by connective tissue cells might concentrate in BL, where their interactions with extracellular matrix proteins might contribute to their effects on the overlying neural tissue, promoting cytogenesis and morphological changes and participating in neuroendocrine regulation.

Animals↗
PubMed2004

Overwhelmingly asynchronous firing of rat subthalamic nucleus neurones in brain slices provides little evidence for intrinsic interconnectivity.

In Parkinson's disease the neurones of the subthalamic nucleus show increased synchrony and oscillatory burst discharge, thought to reflect a breakdown of parallel processing in basal ganglia circuitry. To understand better the mechanisms underlying this transition, we sought to mimic this change in firing pattern within sagittal slices of rat midbrain. The firing patterns of up to four simultaneously extracellularly recorded subthalamic nucleus (STN) neurones were analysed using burst and oscillation detection programs, and correlated activity between pairs of neurones assessed. In control conditions all but 11 of 488 (2%) neurones fired in a predominantly tonic pattern (with mean oscillation frequency >3 Hz), with no significantly cross-correlated activity in any of 393 pairs of neurones. The glutamate antagonists DL-2-amino-phosphonopentanoic acid (APV), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6-methyl-2-(phenylethynyl)pyridine (MPEP) did not change the firing rate or pattern of these cells, providing no evidence for a role of glutamatergic collaterals within the STN under these conditions. The GABA(A) receptor antagonist bicuculline and GABA(B) receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl]phenylmethyl phosphinic acid (CGP 55845) were also without effect on firing rate or pattern in these cells, suggesting that there was no active input from other GABAergic basal ganglia nuclei in this slice. The dopamine receptor antagonist haloperidol caused no significant change to firing rate or pattern of firing in these cells, suggesting that there was no active dopaminergic input in this slice. Excitations of STN neurones by muscarine, (+)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), N-methyl-D-aspartic acid (NMDA) or dopamine were all unaccompanied by a change in firing pattern or any significant correlated activity between STN neurone pairs. Burst firing could be induced in STN neurones with either the potassium channel blocker tetraethylammonium (TEA; 10 mM; in 100/138 [72%] of cells) or with a combination of NMDA and the calcium-activated potassium channel blocker apamin (in 101/216 [47%] of cells). Burst firing in TEA was unchanged by CNOX and APV, MPEP, CGP55845, haloperidol, dopamine, and ACPD, although muscarine produced a significant increase in oscillation frequency. Burst firing in NMDA and apamin was unchanged by CNQX and APV, dopamine, muscarine and ACPD, although bicuculline caused a significant increase in oscillation frequency. Such burst firing was not accompanied by synchrony in any condition, either alone, or during application of excitatory agents or glutamate or GABA antagonists. As the bursting seen here was unaccompanied by the synchronous activity that has often been observed (pathologically) in vivo, it probably reflects solely intrinsic STN neuronal properties, rather than network activity. No functional role was found for glutamatergic collaterals within the STN, either when cells are firing tonically or burst firing. The circuitry needed to produce synchrony in the STN is most likely not intrinsic to the STN itself, but requires connections with other basal ganglia nuclei, and/or the cortex, which are not present in this preparation.

Action Potentials↗
PubMed1992

Spontaneous firing as an epigenetic factor in brain development--physiological consequences of chronic tetrodotoxin and picrotoxin exposure on cultured rat neocortex neurons.

Functional consequences of either suppressing or intensifying spontaneous neuronal firing have been studied in developing rat cerebral cortex cultures using, respectively, tetrodotoxin (TTX) and picrotoxin (PTX) added chronically to the growth medium. Simple measures derived from the interspike interval histogram were able to powerfully discriminate between age and treatment groups. After return to control medium, most TTX-treated neurons spontaneously displayed stereotyped clustering of action potentials ('phasic' firing) which closely resembled the characteristic firing patterns seen acutely in the presence of PTX. The 'TTX-syndrome' thus suggests that GABAergic synaptic inhibition is ineffective in cortical networks grown under conditions which prevent the expression of bioelectric activity. In contrast, after return to control medium, neurons which had been partially disinhibited throughout development (by continuous exposure to PTX) had even less phasic firing than was measured in age-matched controls. Based upon these and previous findings, a two (main) factor model is put forth which can economically account for the major effects. The working hypothesis embodied in this model is that phasic neuronal discharges not only accelerate the maturation of excitatory connections within the neocortex but, even more important, are crucial for the development of adequate inhibitory synaptic transmission.

Animals↗