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Neocortex
Kinds of Neocortex Selected AbstractsArea-Specific Resonance of Excitatory Networks in Neocortex: Control by Outward CurrentsEPILEPSIA, Issue 8 2007Manuel A. Castro-Alamancos Summary:, During disinhibition or low [Mg++]o buffer, 7,14 Hz (,10 Hz) oscillations are generated by excitatory networks of interconnected pyramidal cells in motor (agranular) cortex but are absent in barrel (granular) cortex. Here we studied if the inability of barrel cortex to produce ,10 Hz oscillations during these conditions is because barrel cortex networks lack the necessary cellular mechanisms or, alternatively, because those mechanisms are inhibited by outward currents. The results show that blockers of slowly inactivating voltage-dependent K+ currents unmask ,10 Hz oscillations in barrel cortex, and this occurs in unison with the unmasking of intrinsic inward Ca++ currents that are kept suppressed by the outward currents. Moreover, the ,10 Hz oscillations unmasked in barrel cortex occur independently in upper and lower layers indicating that the ,10 Hz oscillation mechanisms are kept suppressed in multiple networks. The results reveal that the propensity of distinct excitatory networks of neocortex to generate epileptiform oscillatory activities is controlled by outward currents. [source] A Genomic Analysis of Subclinical Hypothyroidism in Hippocampus and Neocortex of the Developing rat BrainJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2009J. E. Royland No abstract is available for this article. [source] Force,frequency and force,length properties in skeletal muscle following unilateral focal ischaemic insult in a rat modelACTA PHYSIOLOGICA, Issue 3 2009G. N. Dormer Abstract Aim:, Our purpose was to quantify skeletal muscle properties following unilateral focal ischaemic insult (stroke) in a rat model. Methods:, Male rats were divided into two groups: stroke and 2 weeks recovery (n = 8) and control group (n = 7). Stroke was induced in the area of the motor neocortex containing hind limb corticospinal neurones. Contractile properties of the medial gastrocnemius muscle were measured in situ in both limbs. Force,length and force,frequency properties were measured before and 35 min after 5 min fatiguing stimulation. Results:, Stroke resulted in bilateral tetanic fade during 200 Hz stimulation. When normalized to 100 Hz contractions, force at 200 Hz was 95.4 ± 0.9% for the paretic muscles, 96.7 ± 1.7% for non-paretic muscles and 102.2 ± 1.0% for muscles of control rats (P = 0.006). Prior to fatiguing contractions, there was no difference in the length dependence of force. During repetitive contractions, active force fell significantly to 19 ± 4 and 25 ± 5% of initial force in paretic and non-paretic muscles of animals with a stroke respectively. In control animals active force fell to 37 ± 5%. During repetitive contractions, fusion index increased in muscles of stroke animals to 1.0 ± 0 but in control animals it was 0.95 ± 0.02. There was selective force depression at short lengths for fatigued paretic muscle (significant difference at muscle lengths less than reference length ,2 mm). Conclusion:, The tetanic fade at high stimulation frequencies indicates that there may be activation failure following focal ischaemic insult. The greater magnitude of fatigue and selective depression at short lengths following repetitive contractions should be investigated further. [source] Genetic manipulation, whole-cell recordings and functional imaging of the sensorimotor cortex of behaving miceACTA PHYSIOLOGICA, Issue 1 2009C. C. H. Petersen Abstract Sensory processing, sensorimotor integration and motor control are amongst the most basic functions of the brain and yet our understanding of how the underlying neuronal networks operate and contribute to behaviour is very limited. The relative simplicity of the mouse whisker sensorimotor system is helpful for detailed quantitative analyses of motor control and perception during active sensory processing. Recent technical advances now allow the measurement of membrane potential in awake-behaving mice, using whole-cell recordings and voltage-sensitive dye imaging. With these recording techniques, it is possible to directly correlate neuronal activity with behaviour. However, in order to obtain causal evidence for the specific contributions of different neuronal networks to behaviour, it is critical to manipulate the system in a highly controlled manner. Advances in molecular neurobiology, gene delivery and mouse genetics provide techniques capable of layer, column and cell-type specific control of gene expression in the mouse neocortex. Over the next years, we anticipate considerable advances in our understanding of brain function through measuring and manipulating neuronal activity with unprecedented precision to probe the molecular and synaptic mechanisms underlying simple forms of active sensory perception and associative learning. [source] Single cause, polymorphic neuronal migration disorders: an animal modelDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2000Glenn D Rosen PhD Injury to the developing cortical plate can result in a variety of neuronal migration disorders. The results are reported of experimental research aimed at determining whether these different types of neocortical malformations are the consequence of comparable injury of varying intensity. Freezing probes were placed on the skulls of 44 newborn rats (age equivalent to 4 to 5 months of gestation in humans) and induced either one or two freezing injuries of durations ranging from 2 to 20 seconds. A variety of cortical malformations including minor laminar dysplasias, molecular layer ectopias, microgyria, and porencephalic cysts were seen in the brains of these animals when they were examined on postnatal day (P)2, P21, and P60. The severity of the malformation was directly related to the strength (number of hits and duration) of the freezing injury. These results suggest that a single etiologic event of varying severity during neuronal migration to the neocortex can induce widely disparate malformations of the cortex. [source] Reelin is essential for neuronal migration but not for radial glial elongation in neonatal ferret cortex,DEVELOPMENTAL NEUROBIOLOGY, Issue 5 2008Alisa Schaefer Abstract Numerous functions related to neuronal migration are linked to the glycoprotein reelin. Reelin also elongates radial glia, which are disrupted in mutant reeler mice. Our lab developed a model of cortical dysplasia in ferrets that shares features with the reeler mouse, including impaired migration of neurons into the cerebral cortex and disrupted radial glia. Explants of normal ferret cortex in coculture with dysplastic ferret cortex restore the deficits in this model. To determine if reelin is integral to the repair, we used explants of P0 mouse cortex either of the wild type (WT) or heterozygous (het) for the reelin gene, as well as P0 reeler cortex (not containing reelin), in coculture with organotypic cultures of dysplastic ferret cortex. This arrangement revealed that all types of mouse cortical explants (WT, het, reeler) elongated radial glia in ferret cortical dysplasia, indicating that reelin is not required for proper radial glial morphology. Migration of cells into ferret neocortex, however, did not improve with explants of reeler cortex, but was almost normal after pairing with WT or het explants. We also placed an exogenous source of reelin in ferret cultures at the pial surface to reveal that migrating cells move toward the reelin source in dysplastic cortex; radial glia in these cultures were also improved toward normal. Our results demonstrate that the normotopic position of reelin is important for proper neuronal positioning, and that reelin is capable of elongating radial glial cells but is not the only radialization factor. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Cooperative activity of multiple upper layer proteins for thalamocortical axon growthDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2008Takuro Maruyama Abstract During development, sensory thalamocortical (TC) axons grow into the neocortex and terminate primarily in layer 4. To study the molecular mechanism that underlies lamina-specific TC axon termination, we investigated the responsiveness of TC axons to ephrin-A5, semaphorin-7A (Sema7A) and kit ligand (KL), which are expressed in the upper layers of the developing cortex. Dissociated cells of the dorsal thalamus from embryonic rat brain were cultured on dishes that were coated with preclustered Fc-tagged extracellular domains of these molecules. Each protein was found to promote TC axon growth in a dose-dependent fashion of a bell-shaped curve. Any combination of the three proteins showed a cooperative effect in lower concentrations but not in higher concentrations, suggesting that their growth-promoting activities act in a common pathway. The effect of spatial distributions of these proteins was further tested on a filter membrane, in which these proteins were printed at a size that recapitulates the scale of laminar thickness in vivo, using a novel protein-printing technique, Simple-To-mAke Micropore Protein-Printing (STAMP2) method. The results demonstrated that TC axons grew massively on the laminin-coated region but were prevented from invading the adjacent ephrin-A5-printed region, suggesting that TC axons detect relative differences in the growth effect between these regions. Moreover, the inhibitory action of ephrin-A5 was enhanced by copresence with KL and Sema7A. Together, these results suggest that the lamina-specific TC axon targeting mechanism involves growth-inhibitory activity by multiple molecules in the upper layers and detection in the molecular environments between the upper and deep layers. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] The effects of social environment on adult neurogenesis in the female prairie voleDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002Christie D. Fowler Abstract In the mammalian brain, adult neurogenesis has been found to occur primarily in the subventricular zone (SVZ) and dentate gyrus of the hippocampus (DG) and to be influenced by both exogenous and endogenous factors. In the present study, we examined the effects of male exposure or social isolation on neurogenesis in adult female prairie voles (Microtus ochrogaster). Newly proliferated cells labeled by a cell proliferation marker, 5-bromo-2,-deoxyuridine (BrdU), were found in the SVZ and DG, as well as in other brain areas, such as the amygdala, hypothalamus, neocortex, and caudate/putamen. Two days of male exposure significantly increased the number of BrdU-labeled cells in the amygdala and hypothalamus in comparison to social isolation. Three weeks later, group differences in BrdU labeling generally persisted in the amygdala, whereas in the hypothalamus, the male-exposed animals had more BrdU-labeled cells than did the female-exposed animals. In the SVZ, 2 days of social isolation increased the number of BrdU-labeled cells compared to female exposure, but this difference was no longer present 3 weeks later. We have also found that the vast majority of the BrdU-labeled cells contained a neuronal marker, indicating neuronal phenotypes. Finally, group differences in the number of cells undergoing apoptosis were subtle and did not seem to account for the observed differences in BrdU labeling. Together, our data indicate that social environment affects neuron proliferation in a stimulus- and site-specific manner in adult female prairie voles. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 115,128, 2002 [source] Sex differences in progesterone receptor immunoreactivity in neonatal mouse brain depend on estrogen receptor , expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Christine K. Wagner Abstract Around the time of birth, male rats express higher levels of progesterone receptors in the medial preoptic nucleus (MPN) than female rats, suggesting that the MPN may be differentially sensitive to maternal hormones in developing males and females. Preliminary evidence suggests that this sex difference depends on the activation of estrogen receptors around birth. To test whether estrogen receptor alpha (ER,) is involved, we compared progesterone receptor immunoreactivity (PRir) in the brains of male and female neonatal mice that lacked a functional ER, gene or were wild type for the disrupted gene. We demonstrate that males express much higher levels of PRir in the MPN and the ventromedial nucleus of the neonatal mouse brain than females, and that PRir expression is dependent on the expression of ER, in these regions. In contrast, PRir levels in neocortex are not altered by ER, gene disruption. The results of this study suggest that the induction of PR via ER, may render specific regions of the developing male brain more sensitive to progesterone than the developing female brain, and may thereby underlie sexual differentiation of these regions. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 176,182, 2001 [source] Peer Commentaries on Marcy A. Kingsbury and Barbara L. Finlay's The cortex in multidimensional space: where do cortical areas come from?DEVELOPMENTAL SCIENCE, Issue 2 2001Article first published online: 28 JUN 200 Elizabeth Bates, Brain evolution and development: passing through the eye of the needle, p. 143 Serena M. Dudek, Multidimensional gene expression in cortical space, p. 145 Henry Kennedy and Colette Dehay, Gradients and boundaries: limits of modularity and its influence on the isocortex, p. 147 Sarah L. Pallas, Specification of mammalian neocortex: the power of the evo,devo approach in resolving the nature,nurture dichotomy, p. 148 Michel Roger, Embryonic stage of commitment of neocortical cells to develop area-specific connections, p. 151 M.W. Spratling and M.H. Johnson, Activity-dependent processes in regional cortical specialization, p. 153 [source] ,-[11C]methyl-L-tryptophan uptake in patients with periventricular nodular heterotopia and epilepsyEPILEPSIA, Issue 5 2008Jun Natsume Summary Background:,-[11C]methyl-L-tryptophan (,-MTrp) positron emission tomography (PET) is a promising tool in the localization of the epileptogenic area in selected group of focal epilepsy patients. Electrophysiological evidence suggests the involvement of the neocortex in periventricular nodular heterotopia (PVNH). Purpose: To determine whether ,-MTrp PET can detect neocortical changes in patients with PVNH. Methods: Four patients (2 male, mean age 28, range 23,35 years) with PVNH and intractable seizures were studied. The functional image in each patient was compared with those from 21 healthy controls (mean age 34.6 ± 14.2 years) by using statistical parametric mapping (SPM). The location of increased ,-MTrp uptake was compared with the location of the EEG focus. A significant cluster was defined as a cluster with a height p = 0.005 and an extent threshold 100. Results:,-MTrp PET revealed increased cortical uptake in two of four patients. The area of increased ,-MTrp uptake in one patient was widespread. In the other patient, the area of increased uptake did not include the region where most seizures were generated on EEG. ,-MTrp PET did not show increased uptake in the heterotopic nodules in any of the patients. Conclusions:,-MTrp PET suggests abnormal metabolism of tryptophan in the neocortex. The increased uptake may be diffuse and may not co-localize with the EEG focus. This preliminary study suggests that ,-MTrp PET may be useful, in conjunction with other evaluations, in localizing epileptic focus in patients with PVNH and refractory seizures. [source] A new animal model of infantile spasms with unprovoked persistent seizuresEPILEPSIA, Issue 2 2008Chong L. Lee Summary Purpose: Infantile spasms is one of the most severe epileptic syndromes of infancy and early childhood. Progress toward understanding the pathophysiology of this disorder and the development of effective therapies has been hindered by the lack of a relevant animal model. We report here the creation of such a model. Methods: The sodium channel blocker, tetrodotoxin (TTX), was chronically infused into the developing neocortex or hippocampus of infant rats by way of an osmotic minipump starting on postnatal day 10,12. Results: After a minimum of 10 days of infusion, approximately one-third of these rats began to display very brief (1,2 s) spasms, which consisted of symmetric or asymmetric flexion or extension of the trunk and sometimes involvement of one or both forelimbs. The typical ictal EEG pattern associated with the behavioral spasms consisted of an initial generalized, high amplitude, slow wave followed by an electrodecrement with superimposed fast activity. The interictal EEG revealed multifocal spikes and sharp waves, and in most animals that had spasms a hypsarrhythmic pattern was seen, at least intermittently, during NREM sleep. Like in humans, the spasms in the rat often occurred in clusters especially during sleep,wake transitions. Comparison of the ictal and interictal EEGs recorded in this model and those from humans with infantile spasms revealed that the patterns and the frequency components of both the ictal events and hypsarrhythmia were very similar. Discussion: The TTX model of infantile spasms should be of value in furthering an understanding of the pathophysiology of this seizure disorder. [source] Area-Specific Resonance of Excitatory Networks in Neocortex: Control by Outward CurrentsEPILEPSIA, Issue 8 2007Manuel A. Castro-Alamancos Summary:, During disinhibition or low [Mg++]o buffer, 7,14 Hz (,10 Hz) oscillations are generated by excitatory networks of interconnected pyramidal cells in motor (agranular) cortex but are absent in barrel (granular) cortex. Here we studied if the inability of barrel cortex to produce ,10 Hz oscillations during these conditions is because barrel cortex networks lack the necessary cellular mechanisms or, alternatively, because those mechanisms are inhibited by outward currents. The results show that blockers of slowly inactivating voltage-dependent K+ currents unmask ,10 Hz oscillations in barrel cortex, and this occurs in unison with the unmasking of intrinsic inward Ca++ currents that are kept suppressed by the outward currents. Moreover, the ,10 Hz oscillations unmasked in barrel cortex occur independently in upper and lower layers indicating that the ,10 Hz oscillation mechanisms are kept suppressed in multiple networks. The results reveal that the propensity of distinct excitatory networks of neocortex to generate epileptiform oscillatory activities is controlled by outward currents. [source] Cerebral Damage in Epilepsy: A Population-based Longitudinal Quantitative MRI StudyEPILEPSIA, Issue 9 2005Rebecca S. N. Liu Summary:,Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community-based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex. Methods: One hundred seventy-nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times. Results: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy. Conclusions: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age-related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures. [source] Characterization of the Tetanus Toxin Model of Refractory Focal Neocortical Epilepsy in the RatEPILEPSIA, Issue 2 2005Karen E. Nilsen Summary:,Purpose: To characterize in detail a model of focal neocortical epilepsy. Methods: Chronic focal epilepsy was induced by injecting 25,50 ng of tetanus toxin or vehicle alone (controls) into the motor neocortex of rats. EEG activity was recorded from electrodes implanted at the injection site, along with facial muscle electromyographic (EMG) activity and behavioral monitoring intermittently for up to 5 months in some animals. Drug responsiveness was assessed by using the antiepileptic drugs (AEDs) diazepam (DZP) and phenytoin (PHT) delivered systemically, while 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), a competitive antagonist at AMPA receptors, was administered directly to the brain to investigate the potential benefits of focal drug delivery. Results: Tetanus toxin induced mild behavioral seizures that persisted indefinitely in all animals. EEG spiking activity, occurring up to 80% of the time, correlated with clinical seizures consisting of interrupted behavioral activity, rhythmic bilateral facial twitching, and periods of abrupt motor arrest. Seizures were refractory to systemic administration of DZP and PHT. However, focal delivery of NBQX to the seizure site reversibly reduced EEG and behavioral seizure activity without detectable side effects. Conclusions: This study provides a long-term detailed characterisation of the tetanus toxin model. Spontaneous, almost continuous, well-tolerated seizures occur and persist, resembling those seen in neocortical epilepsy, including cortical myoclonus and epilepsia partialis continua. The seizures appear to be similarly resistant to conventional AEDs. The consistency, frequency, and clinical similarity of the seizures to refractory epilepsy in humans make this an ideal model for investigation of both mechanisms of seizure activity and new therapeutic approaches. [source] Heat Shock Protein-27 Is Upregulated in the Temporal Cortex of Patients with EpilepsyEPILEPSIA, Issue 12 2004Hans-J Bidmon Summary:,Purpose: Heat shock protein-27 (HSP-27) belongs to the group of small heat shock proteins that become induced in response to various pathologic conditions. HSP-27 has been shown to protect cells and subcellular structures, particularly mitochondria, and serves as a carrier for estradiol. It is a reliable marker for tissues affected by oxidative stress. Oxidative stress and related cellular defence mechanisms are currently thought to play a major role during experimentally induced epileptic neuropathology. We addressed the question whether HSP-27 becomes induced in the neocortex resected from patients with pharmacoresistant epilepsy. Methods: Human epileptic temporal neocortex was obtained during neurosurgery, and control tissue was obtained at autopsy from subjects without known neurologic diseases. The tissues were either frozen for Western blot analysis or fixed in Zamboni's fixative for the topographic detection of HSP-27 at the cellular level by means of immunohistochemistry. Results: HSP-27 was highly expressed in all epilepsy specimens and in the cortex of a patient who died in the final stage of multiple sclerosis (positive control), whereas only low amounts of HSP-27 were detectable in control brains. In epilepsy patients, HSP-27 was present in astrocytes and in the walls of blood vessels. The intracortical distribution patterns varied strongly among the epilepsy specimens. Conclusions: These results demonstrate that HSP-27 becomes induced in response to epileptic pathology. Although the functional aspects of HSP-27 induction during human epilepsy have yet to be elucidated, it can be concluded that HSP-27 is a marker for cortical regions in which a stress response has been caused by seizures. [source] Effects of Antiepileptic Drugs on Refractory Seizures in the Intact Immature Corticohippocampal Formation In VitroEPILEPSIA, Issue 11 2003Pascale Paule Quilichini Summary:,Purpose: We developed a new in vitro preparation of immature rats, in which intact corticohippocampal formations (CHFs) depleted in magnesium ions become progressively epileptic. The better to characterize this model, we examined the effects of 14 antiepileptic drugs (AEDs) currently used in clinical practice. Methods: Recurrent ictal-like seizures (ILEs, four per hour) were generated in intact CHFs of P7,8 rats, and extracellular recordings were performed in the hippocampus and neocortex. AEDs were applied at clinically relevant concentrations (at least two), during 30 min after the third ILE. Their ability to prevent or to delay the next ILE was examined. Results: Valproic acid and benzodiazepines (clobazam and midazolam) but also phenobarbital and levetiracetam prevent the occurrence of seizures. In contrast, usual concentrations of carbamazepine (CBZ), phenytoin, vigabatrin, tiagabine, gabapentin, lamotrigine (LTG), topiramate, felbamate, and ethosuximide did not suppress ILEs. In addition, LTG and CBZ aggravate seizures in one third of the cases. Conclusions: This intact in vitro preparation in immature animals appears to be quite resistant to most AEDs. Blockade of seizures was achieved with drugs acting mainly at the ,-aminobutyric acid (GABA)A -receptor site but not with those that increase the amount of GABA. Drugs with a broad spectrum of activity are efficient but not those preferentially used in partial seizures or absences. We suggest that this preparation may correspond to a model of epilepsy with generalized convulsive seizures and could be helpful to develop new AEDs for refractory infantile epilepsies. [source] Epilepsy-induced Changes in Signaling Systems of Human and Rat Postsynaptic DensitiesEPILEPSIA, Issue 2 2003Ursula Wyneken Summary: ,Purpose: To study seizure-induced changes in signaling proteins present in postsynaptic densities (PSDs) isolated from human epileptic neocortex and from rat cortex in which seizures were induced by injection of kainic acid. Methods: We performed Western blot analysis of signaling proteins in PSDs isolated from cortical tissue. Results: Seizures induce a strong upregulation of TrkB, the receptor for brain-derived neurotrophic factor (BDNF), whereas components of the N -methyl- d -aspartate (NMDA)-receptor complex are downregulated in both human and rat PSDs. Conclusions: These data show that long-term changes in PSD composition occur as a consequence of epileptic seizure activity. [source] Increased Expression of the Neuronal Glutamate Transporter (EAAT3/EAAC1) in Hippocampal and Neocortical EpilepsyEPILEPSIA, Issue 3 2002Peter B. Crino Summary: ,Purpose: To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy. Methods: The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine-induced temporal lobe epilepsy (TLE) and age-matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis. Results: The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with nondysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT-1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue. Conclusions: Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types. [source] Distribution and Initiation of Seizure Activity in a Rat Brain with Subcortical Band HeterotopiaEPILEPSIA, Issue 5 2000Zong-Fu Chen Summary: Purpose: Misplaced (heterotopic) cortical neurons are a common feature of developmental epilepsies. To better understand seizure disorders associated with cortical heterotopia, the sites of aberrant discharge activity were investigated in vivo and in vitro in a seizure-prone mutant rat (tish) exhibiting subcortical band heterotopia. Methods: Depth electrode recordings and postmortem assessment of regional c- fos mRNA levels were used to characterize the distribution of aberrant discharge activity during spontaneous seizures in vivo. Electrophysiologic recordings of spontaneous and evoked activity also were performed by using in vitro brain slices from the tish rat treated with proconvulsant drugs (penicillin and 4-aminopyridine). Results: Depth electrode recordings demonstrate that seizure activity begins almost simultaneously in the normotopic and heterotopic areas of the tish neocortex. Spontaneous seizures induce c- fos mRNA in normotopic and heterotopic neocortical areas, and limbic regions. The threshold concentrations of proconvulsant drugs for inducing epileptiform spiking were similar in the normotopic and heterotopic areas of tish brain slices. Manipulations that blocked communication between the normotopic and heterotopic areas of the cortex inhibited spiking in the heterotopic, but not the normotopic, area of the cortex. Conclusions: These findings indicate that aberrant discharge activity occurs in normotopic and heterotopic areas of the neocortex, and in certain limbic regions during spontaneous seizures in the tish rat. Normotopic neurons are more prone to exhibit epileptiform activity than are heterotopic neurons in the tish cortex, and heterotopic neurons are recruited into spiking by activity initiated in normotopic neurons. The findings indicate that seizures in the tish brain primarily involve telencephalic structures, and suggest that normotopic neurons are responsible for initiating seizures in the dysplastic neocortex. [source] Long-range connectivity of mouse primary somatosensory barrel cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2010Rachel Aronoff Abstract The primary somatosensory barrel cortex processes tactile vibrissae information, allowing rodents to actively perceive spatial and textural features of their immediate surroundings. Each whisker on the snout is individually represented in the neocortex by an anatomically identifiable ,barrel' specified by the segregated termination zones of thalamocortical axons of the ventroposterior medial nucleus, which provide the primary sensory input to the neocortex. The sensory information is subsequently processed within local synaptically connected neocortical microcircuits, which have begun to be investigated in quantitative detail. In addition to these local synaptic microcircuits, the excitatory pyramidal neurons of the barrel cortex send and receive long-range glutamatergic axonal projections to and from a wide variety of specific brain regions. Much less is known about these long-range connections and their contribution to sensory processing. Here, we review current knowledge of the long-range axonal input and output of the mouse primary somatosensory barrel cortex. Prominent reciprocal projections are found between primary somatosensory cortex and secondary somatosensory cortex, motor cortex, perirhinal cortex and thalamus. Primary somatosensory barrel cortex also projects strongly to striatum, thalamic reticular nucleus, zona incerta, anterior pretectal nucleus, superior colliculus, pons, red nucleus and spinal trigeminal brain stem nuclei. These long-range connections of the barrel cortex with other specific cortical and subcortical brain regions are likely to play a crucial role in sensorimotor integration, sensory perception and associative learning. [source] Excitatory actions of substance P in the rat lateral posterior nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2010Kush Paul Abstract The lateral posterior nucleus (LP) receives inputs from both neocortex and superior colliculus (SC), and is involved with integration and processing of higher-level visual information. Relay neurons in LP contain tachykinin receptors and are innervated by substance P (SP)-containing SC neurons and by layer V neurons of the visual cortex. In this study, we investigated the actions of SP on LP relay neurons using whole-cell recording techniques. SP produced a graded depolarizing response in LP neurons along the rostro-caudal extent of the lateral subdivision of LP nuclei (LPl), with a significantly larger response in rostral LPl neurons compared with caudal LPl neurons. In rostral LPl, SP (5,2000 nm) depolarized nearly all relay neurons tested (> 98%) in a concentration-dependent manner. Voltage-clamp experiments revealed that SP produced an inward current associated with a decreased conductance. The inward current was mediated primarily by neurokinin receptor (NK)1 tachykinin receptors, although significantly smaller inward currents were produced by specific NK2 and NK3 receptor agonists. The selective NK1 receptor antagonist RP67580 attenuated the SP-mediated response by 71.5% and was significantly larger than the attenuation of the SP response obtained by NK2 and NK3 receptor antagonists, GR159897 and SB222200, respectively. The SP-mediated response showed voltage characteristics consistent with a K+ conductance, and was attenuated by Cs+, a K+ channel blocker. Our data suggest that SP may modulate visual information that is being processed and integrated in the LPl with inputs from collicular sources. [source] Recruiting new neurons from the subventricular zone to the rat postnatal cortex: an organotypic slice culture modelEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2008A. G. Dayer Abstract The neurogenic subventricular zone (SVZ) of the lateral ventricle is a potential source for neuronal replacement in the postnatal or adult neocortex after injury. Here we present a novel model system to directly explore the cellular mechanisms of this process. In order to visualize directed migration from the SVZ towards the cortex, we transplanted green fluorescent protein-labeled progenitor/stem cells into the SVZ of newborn rats. At 2 days after transplantation, we generated organotypic slice cultures and applied fluorescent time-lapse imaging to explore directly the migration and integration of donor cells into the host tissue for up to 2 weeks. Our studies revealed that subventricular grafts provide a significant number of immature neurons to neocortical regions. In the cortex, immature neurons first migrate radially towards the pial surface and then differentiate into GABAergic interneurons. We conclude that our model system presents a novel and effective experimental paradigm to evaluate the recruitment of SVZ-derived neurons into the postnatal cortex, a phenomenon that may represent a potential route for cortical repair. [source] Multi-directional differentiation of doublecortin- and NG2-immunopositive progenitor cells in the adult rat neocortex in vivoEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Yasuhisa Tamura Abstract In the adult mammalian brain, multipotent stem or progenitor cells involved in reproduction of neurons and glial cells have been well investigated only in very restricted regions; the subventricular zone of the lateral ventricle and the dentate gyrus in the hippocampal formation. In the neocortex, a series of in vitro studies has suggested the possible existence of neural progenitor cells possessing neurogenic and/or gliogenic potential in adult mammals. However, the cellular properties of the cortical progenitor cells in vivo have not been fully elucidated. Using 5,-bromodeoxyuridine labeling and immunohistochemical analysis of cell differentiation markers, we found that a subpopulation of NG2-immunopositive cells co-expressing doublecortin (DCX), an immature neuron marker, ubiquitously reside in the adult rat neocortex. Furthermore, these cells are the major population of proliferating cells in the region. The DCX(+)/NG2(+) cells reproduced the same daughter cells, or differentiated into DCX(+)/NG2(,) (approximately 1%) or DCX(,)/NG2(+) (approximately 10%) cells within 2 weeks after cell division. The DCX(+)/NG2(,) cells were also immunopositive for TUC-4, a neuronal linage marker, suggesting that these cells were committed to neuronal cell differentiation, whereas the DCX(,)/NG2(+) cells showed faint immunoreactivity for glutathione S-transferase (GST)-pi, an oligodendrocyte lineage marker, in the cytoplasm, suggesting glial cell lineage, and thereafter the cells differentiated into NG2(,)/GST-pi(+) mature oligodendrocytes after a further 2 weeks. These findings indicate that DCX(+)/NG2(+) cells ubiquitously exist as ,multipotent progenitor cells' in the neocortex of adult rats. [source] Synchrony of spontaneous calcium activity in mouse neocortex before synaptogenesisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Jean-Claude Platel Abstract Spontaneous calcium activity can be detected in embryonic mouse cortical slices as fluorescence intensity variations, in the presence of a fluorescent calcium indicator. Current methods to detect and quantify these variations depend heavily on experimenters whose judgement may interfere with measurement. In the present work, we developed new software called CalSignal for automatic detection and tracking of cellular bodies and quantification of spontaneous calcium activity on time-series of confocal fluorescence images. Analysis of 28 neocortical slices revealed that 21.0% of detected cells displayed peaks of fluorescence corresponding to spontaneous activity, with a mean frequency of one peak per 4 min. This activity was blocked in the absence of extracellular calcium but was not modified after depletion of calcium stores with thapsigargin or blockade of voltage-gated calcium channels with Ni2+. Further, statistical analysis of calcium activity revealed concomitant activation of distant cells in 24 slices, and the existence of a significant network of synchrony based on such coactivations in 17 slices out of 28. These networks enclosed 84.3% of active cells, scattered throughout the neocortical wall (mean distance between cellular bodies, 111.7 µm). Finally, it was possible to identify specific cells which were synchronously active with more neighbouring cells than others. The identity of these nodal cells remains to be investigated to fully comprehend the role of spontaneous calcium activity, before synaptogenesis, in shaping cortical neurogenesis. [source] Impact of S100B on local field potential patterns in anesthetized and kainic acid-induced seizure conditions in vivoEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Seiichi Sakatani Abstract S100B is a calcium-binding protein predominantly expressed in astrocytes. Previous studies using gene-manipulated animals have suggested that the protein has a role in synaptic plasticity and learning. In order to assess the physiological roles of the protein in active neural circuitry, we recorded spontaneous neural activities from various layers of the neocortex and hippocampus in urethane-anesthetized S100B knockout (KO) and wildtype (WT) control mice. Typical local field oscillation patterns including the slow (0.5,2 Hz) oscillations in the neocortex, theta (3,8 Hz) and sharp wave-associated ripple (120,180 Hz) oscillations in the hippocampus were observed in both genotypes. Comparisons of the frequency, power and peak amplitude have shown that these oscillatory patterns were virtually indistinguishable between WT and KO. When seizure was induced by intraperitoneal injection of kainic acid, a difference between WT and KO appeared in the CA1 radiatum local field potential pattern, where seizure events were characterized by prominent appearance of hyper-synchronous gamma band (30,80 Hz) activity. Although both genotypes developed seizures within 40 min, the gamma amplitude was significantly smaller during the development of seizures in KO mice. Our results suggest that deficiency of S100B does not have a profound impact on spontaneous neural activity in normal conditions. However, when neural activity was sufficiently raised, activation of S100B-related pathways may take effect, resulting in modulation of neural activities. [source] Visualization of corticofugal projections during early cortical development in a ,-GFP-transgenic mouseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007Erin C. Jacobs Abstract The first postmitotic neurons in the developing neocortex establish the preplate layer. These early-born neurons have a significant influence on the circuitry of the developing cortex. However, the exact timing and trajectory of their projections, between cortical hemispheres and intra- and extra-cortical regions, remain unresolved. Here, we describe the creation of a transgenic mouse using a 1.3 kb golli promoter element of the myelin basic protein gene to target expression of a ,,green fluorescent protein (GFP) fusion protein in the cell bodies and processes of pioneer cortical neurons. During embryonic and early neonatal development, the timing and patterning of process extension from these neurons was examined. Analysis of ,-GFP fluorescent fibers revealed that progression of early labeled projections was interrupted unexpectedly by transient pauses at the corticostriatal and telencephalic,diencephalic boundaries before invading the thalamus just prior to birth. After birth the pioneering projections differentially invaded the thalamus, excluding some nuclei, e.g. medial and lateral geniculate, until postnatal days 10,14. Early labeled projections were also found to cross to the contralateral hemisphere as well as to the superior colliculus. These results indicate that early corticothalamic projections appear to pause before invading specific subcortical regions during development, that there is developmental regulation of innervation of individual thalamic nuclei, and that these early-generated neurons also establish early projections to commissural and subcortical targets. [source] Elements of a neurobiological theory of hippocampal function: the role of synaptic plasticity, synaptic tagging and schemasEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006R. G. M. MorrisArticle first published online: 8 JUN 200 Abstract The 2004 EJN Lecture was an attempt to lay out further aspects of a developing neurobiological theory of hippocampal function [Morris, R.G.M., Moser, E.I., Riedel, G., Martin, S.J., Sandin, J., Day, M. & O'Carroll, C. (2003) Phil. Trans. R. Soc. Lond. B Biol. Sci., 358, 773,786.] These are that (i) activity-dependent synaptic plasticity plays a key role in the automatic encoding and initial storage of attended experience; (ii) the persistence of hippocampal synaptic potentiation over time can be influenced by other independent neural events happening closely in time, an idea with behavioural implications for memory; and (iii) that systems-level consolidation of memory traces within neocortex is guided both by hippocampal traces that have been subject to cellular consolidation and by the presence of organized schema in neocortex into which relevant newly encoded information might be stored. Hippocampal memory is associative and, to study it more effectively than with previous paradigms, a new learning task is described which is unusual in requiring the incidental encoding of flavour,place paired associates, with the readout of successful storage being successful recall of a place given the flavour with which it was paired. NMDA receptor-dependent synaptic plasticity is shown to be critical for the encoding and intermediate storage of memory traces in this task, while AMPA receptor-mediated fast synaptic transmission is necessary for memory retrieval. Typically, these rapidly encoded traces decay quite rapidly over time. Synaptic potentiation also decays rapidly, but can be rendered more persistent by a process of cellular consolidation in which synaptic tagging and capture play a key part in determining whether or not it will be persistent. Synaptic tags set at the time of an event, even many trivial events, can capture the products of the synthesis of plasticity proteins set in train by events before, during or even after an event to be remembered. Tag,protein interactions stabilize synaptic potentiation and, by implication, memory. The behavioural implications of tagging are explored. Finally, using a different protocol for flavour,place paired associate learning, it is shown that rats can develop a spatial schema which represents the relative locations of several different flavours of food hidden at places within a familiar space. This schema is learned gradually but, once acquired, enables new paired associates to be encoded and stored in one trial. Their incorporation into the schema prevents rapid forgetting and suggests that schema play a key and hitherto unappreciated role in systems-level memory consolidation. The elements of what may eventually mature into a more formal neurobiological theory of hippocampal memory are laid out as specific propositions with detailed conceptual discussion and reference to recent data. [source] Effect of cortical spreading depression on synaptic transmission of rat hippocampal tissuesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006Brigitta Wernsmann Abstract Cortical spreading depression (CSD) is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain. In vitro and ex vivo/in vitro brain slice techniques were used to investigate CSD effects on the field excitatory postsynaptic potentials (fEPSP) and tetanus-induced long-term potentiation (LTP) in combined rat hippocampus,cortex slices. Induction of CSD in combined hippocampus,cortex slices in which DC negative deflections did not propagate from neocortex to hippocampus significantly augmented fEPSP amplitude and LTP in the hippocampus. Propagation of CSD to the hippocampus resulted in a transient suppression followed by reinstatement of fEPSP with amplitude of pre-CSD levels. LTP was inhibited when DC potential shifts were recorded in the hippocampus. Furthermore, CSD was induced in anaesthetized rats and, thereafter, hippocampal tissues were examined in vitro. LTP was significantly enhanced in hippocampal slices obtained from ipsilateral site to the hemisphere in which CSD was evoked. The results indicate the disturbances of hippocampal synaptic transmission triggered by propagation of CSD. This perturbation of hippocampal synaptic transmission induced by CSD may relate to some symptoms occurring during migraine attacks, such as amnesia and hyperactivity. [source] Depression of retinogeniculate synaptic transmission by presynaptic D2 -like dopamine receptors in rat lateral geniculate nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006G. Govindaiah Abstract Extraretinal projections onto neurons in the dorsal lateral geniculate nucleus (dLGN) play an important role in modifying sensory information as it is relayed from the visual thalamus to neocortex. The dLGN receives dopaminergic innervation from the ventral tegmental area; however, the role of dopamine in synaptic transmission in dLGN has not been explored. In the present study, whole cell recordings were obtained to examine the actions of dopamine on glutamatergic synaptic transmission. Dopamine (2,100 µm) strongly suppressed excitatory synaptic transmission in dLGN relay neurons that was evoked by optic tract stimulation and mediated by both N -methyl- d -aspartate and non -N -methyl- d -aspartate glutamate receptors. In contrast, dopamine did not alter inhibitory synaptic transmission arising from either dLGN interneurons or thalamic reticular nucleus neurons. The suppressive action of dopamine on excitatory synaptic transmission was mimicked by the D2 -like dopamine receptor agonist bromocriptine (2,25 µm) but not by the D1 -like receptor agonist SKF38393 (10,25 µm). In addition, the dopamine-mediated suppression was antagonized by the D2 -like receptor antagonist sulpiride (10,20 µm) but not by the D1 -like receptor antagonist SCH23390 (5,25 µm). The dopamine-mediated decrease in evoked excitatory postsynaptic current amplitude was accompanied by an increase in the magnitude of paired-pulse depression. Furthermore, dopamine also reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. Taken together, these data suggest that dopamine may act presynaptically to regulate the release of glutamate at the retinogeniculate synapse and modify transmission of visual information in the dLGN. [source] | |||||||||||||||||||||||||||||||