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Sensitivity to auditory object features in human temporal neocortex.

This positron emission tomography study examined the hemodynamic response of the human brain to auditory object feature processing. A continuum of object feature variation was created by combining different numbers of stimuli drawn from a diverse sample of 45 environmental sounds. In each 60 sec scan condition, subjects heard either a distinct individual sound on each trial or simultaneous combinations of sounds that varied systematically in their similarity or distinctiveness across conditions. As more stimuli are combined they become more similar and less distinct from one another; the limiting case is when all 45 are added together to form a noise that is repeated on each trial. Analysis of covariation of cerebral blood flow elicited by this parametric manipulation revealed a response in the upper bank of the right anterior superior temporal sulcus (STS): when sounds were identical across trials (i.e., a noise made up of 45 sounds), activity was at a minimum; when stimuli were different from one another, activity was maximal. A right inferior frontal area was also revealed. The results are interpreted as reflecting sensitivity of this region of temporal neocortex to auditory object features, as predicted by neurophysiological and anatomical models implicating an anteroventral functional stream in object processing. The findings also fit with evidence that voice processing may involve regions within the anterior STS. The data are discussed in light of these models and are related to the concept that this functional stream is sensitive to invariant sound features that characterize individual auditory objects.

Acoustic Stimulation↗

Induced minor malformations in the neocortex of normal mice do not alter immunological functions.

The interactive relationship between the CNS and the immune system is well established. Major lesions in the brain have been shown to affect immune response. However, whether minor, focal lesions (ectopias), as seen in autoimmune mice, may induce alterations in the immune system is unknown. To address this point, ectopic lesions in the neocortex were induced in neonatal DBA/2 mice (Induced minor malformations; IMM) and their immune capabilities were assessed at adulthood. Serum was collected from each animal and analyzed for the presence of autoantibodies. In addition, splenic lymphocytes and thymocytes were collected to ascertain proliferative capabilities and to assess for possible phenotypic changes in lymphocyte subsets. Mice with IMM did not manifest IgG autoantibodies against cardiolipin, dsDNA or brain membrane antigens. Total lymphocyte cellularity was not affected. The induction of cerebrocortical ectopias did not impair the ability of splenic and thymic lymphocytes to proliferate in response to anti-CD3 antibodies or Concanavalin-A (Con-A) as determined by non-radioactive (Alamar Blue) and radioactive (3H-thymidine) assays. Moreover, no difference in proliferation of unstimulated and anti-CD3-stimulated splenic lymphocytes exposed to rIL-2 or rIL-7 was observed. Flow cytomeric analysis of a variety of cell surface antigens, indicated that there was no difference in lymphocyte subsets between control and IMM groups. Therefore, we conclude that induced IMM lesions in the CNS of normal DBA/2 mice do not alter immune functions.

Animals↗

Early changes in neurons of the hippocampus and neocortex in transgenic rats expressing intracellular human a-beta.

Alzheimer's disease (AD) studies typically focus on the extracellular impact of the amyloid-beta (Abeta) protein, however recent findings also implicate intracellular Abeta (iAbeta) accumulation in the disease's molecular neuropathology. In a double mutant transgenic rat model (AbetaPP and PS1 mutations, UKUR25), stably expressing intracellular human Abeta fragments in an environment devoid of both amyloid plaques and neurofibrillary tangles, we investigated the impact of iAbeta burden on both the incidence and relative cross sectional areas of the Golgi apparatus, lysosomes and lipofuscin bodies. Pyramidal cells within the hippocampus and neocortex of both transgenic and non-transgenic age matched controls were compared. This comparison revealed a significant increase in both the proportional area occupied by Golgi apparatus elements as well as in the mean individual cross sectional area of Golgi compartments in the hippocampus of transgenic rats as compared to controls. Elevated lysosome and lipofuscin elements in the hippocampi of transgenic rats were observed, as was an increase in the mean individual, cross sectional area of lipofuscin bodies in the cortex of transgenic rats as compared to controls. These findings support the hypothesis that intracellular Abeta accumulation not only has an impact on subcellular compartments but also potentially contributes to the neuronal cell pathology observed in AD.

Alzheimer Disease↗

The spatial dimensions of electrically coupled networks of interneurons in the neocortex.

Inhibitory interneurons of the neocortex are electrically coupled to cells of the same type through gap junctions. We studied the spatial organization of two types of interneurons in the rat somatosensory cortex: fast-spiking (FS) parvalbumin-immunoreactive (PV+) cells, and low threshold-spiking (LTS) somatostatin-immunoreactive (SS+) cells. Paired recordings in layer 4 demonstrated that both the probability of coupling and the coupling coefficient drop steeply with intersomatic distance, reaching zero beyond 200 microm. The dendritic arbors of FS and LTS cells were reconstructed from electrophysiologically characterized, biocytin-filled cells; the two cell types had only minor differences in the number and span of their dendrites. However, there was a markedly higher density of PV+ cells than SS+ cells. PV+ cells were densest in layer 4, while SS+ cell density peaked in the subgranular layers. From these data we estimate that there is measurable electrical coupling (directly or indirectly via intermediary cells) between each interneuron and 20-50 others. The large number of electrical synapses implies that each interneuron participates in a large, continuous syncytium. To evaluate the functional significance of these findings, we examined several simple architectures of coupled networks analytically. We present a mathematical method to estimate the average summated coupling conductance that each cell receives from all of its neighbors, and the average leak conductance of individual cells, and we suggest that these have the same order of magnitude. These quantitative results have important implications for the effects of electrical coupling on the dynamic behavior of interneuron networks.

Action Potentials↗

Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep.

To clarify the neural correlates and brain activity during the progression of human non-rapid eye movement (NREM) sleep, we examined the absolute regional cerebral blood flow (rCBF) during light and deep NREM sleep and during wakefulness in normal humans using positron emission tomography with H(2)(15)O. Relative changes in rCBF during light and deep NREM sleep in comparison to the rCBF during wakefulness were also analyzed. During light NREM sleep, the rCBF in the midbrain, in contrast to that in the pons and thalamic nuclei, did not decrease when compared to that during wakefulness, whereas rCBF decreased in the left medial frontal gyrus, left inferior frontal gyrus, and left inferior parietal gyrus of the neocortex. During deep NREM sleep, the rCBF in the midbrain tegmentum decreased, and there was a marked and bilateral decrease in the rCBF in all neocortical regions except for the perirolandic areas and the occipital lobe. There have been three groups of brain structures, each representing one type of deactivation during the progression of NREM sleep. The activity of the midbrain reticular formation is maintained during light NREM sleep and therefore represents a key distinguishing characteristic between light and deep NREM sleep. Selective deactivation of heteromodal association cortices, including those related to language, occurs with increasingly deep NREM sleep, which supports the recent theory that sleep is not a global, but it is a local process of the brain.

Adult↗

[Unified postsynaptic mechanism of plasticity in the striatum, neocortex, hippocampus, and cerebellum].

The unitary postsynaptic mechanism of plasticity in striatum, neocortex, hippocampus and cerebellum involves the LTP/LTD excitation as result of AMPA and NMDA receptor phosphorylation/dephosphorylation, while the LTP/LTD of inhibition is the result of the GABA receptor phosphorylation/dephosphorylation. It follows from this mechanism that when NMDA channels are closed, the determinant role in receptor phosphorylation is played by the PKG. When the NMDA channels are open, the determinant role in receptor phosphorylation is played by the PKC and CaMKII.

Animals↗

[Effect of sodium nitrite on the activity of the neocortex neurons during realization of defense and inhibition conditioned reflexes].

A decrease in intensity and duration of short-latency reaction components of the sensorimotor and visual cortical neurons to specific stimuli (pain reinforcement and light flashes, respectively) was observed after the administration of NO-generating sodium nitrite (11 mg/kg, subcutaneously). Activation decrease in the visual cortex took place irrespective of biological significance of the light flashes, i.e., in case when this stimulus was a signal of defensive conditioning and in case when these flashes were applied with continuous light (a conditioned inhibitor). Sodium nitrite almost did not change the late activation of sensorimotor and visual neurons in response to pain reinforcement and disinhibitory action of the latter. The results confirm the viewpoint about different neurotransmitters in "specifically modal" and "non-specific" pathways to the neocortex during learning.

Animals↗

Kainate receptors regulate unitary IPSCs elicited in pyramidal cells by fast-spiking interneurons in the neocortex.

Unitary IPSCs elicited by fast-spiking (FS) interneurons in layer V pyramidal cells of the neocortex were studied by means of dual whole-cell recordings in acute slices. FS to pyramidal cell unitary IPSCs were depressed by (RS)-S-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) (ATPA), a kainate (KA) receptor agonist, and by the endogenous agonist l-glutamate in the presence of AMPA, NMDA, mGluR, and GABA(B) receptor antagonists. This effect was accompanied by an increase in failure rate of synaptic transmission, in the coefficient of variation, and in the paired pulse ratio, indicating a presynaptic origin of the IPSC depression. Pairing the activation of the presynaptic neuron with a depolarization of the postsynaptic cell mimicked the decrease of unitary IPSCs, and this effect persisted when postsynaptic sodium action potentials were blocked with the local anesthetic QX314. The effects of ATPA, glutamate, and of the pairing protocol were almost totally blocked by CNQX. These data suggest that KA receptors located on presynaptic FS cell terminals decrease the release of GABA and can be activated by glutamate released from the somatodendritic compartment of the postsynaptic pyramidal cells.

Action Potentials↗

A novel role of vasopressin in the brain: modulation of activity-dependent water flux in the neocortex.

The brain contains an intrinsic vasopressin fiber system the function of which is unknown. It has been demonstrated recently that astrocytes express high levels of a water channel, aquaporin-4 (AQP4). Because vasopressin is known to regulate aquaporin expression and translocation in kidney collecting ducts and thereby control water reabsorption, we hypothesized that vasopressin might serve a similar function in the brain. By recording intrinsic optical signals in an acute cortical slice preparation we showed that evoked neuronal activity generates a radial water flux in the neocortex. The rapid onset and high capacity of this flux suggest that it is mediated through the AQP4-containing astrocytic syncytium that spans the entire thickness of the neocortical mantle. Vasopressin and vasopressin receptor V1a agonists were found to facilitate this flux. V1a antagonists blocked the facilitatory effect of vasopressin and reduced the water flux even in the absence of any exogenous agonist. V2 agonists or antagonists had no effect. These data suggest that vasopressin and V1a receptors play a crucial role in the regulation of brain water and ion homeostasis, most probably by modulating aquaporin-mediated water flux through astrocyte plasma membranes.

Animals↗

Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy.

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease.

Adolescent↗

[Initial stages of differentiation of pyramidal neurons in deep layers of the mouse neocortex in the prenatal period].

The time of initiation of neuron differentiation in deep neocortical layers was determined in mouse embryos and total effect of ionizing radiation on the developing mouse brain was evaluated. The population of cells that form layers V and VI with differentiation occurring in a half of them was shown to be present in mice embryos on d13. This population comprises both non differentiated neuroblasts and juvenile neurons of certain level of differentiation. They make the half of total population and their number remains unchanged on d14. Irradiation of mouse embryos at early postimplantation stage (d12) causes severe disturbances of neocortex development that are conditioned by massive cell death, abnormal development of all the brain structures and reduction of brain volume. Irradiation of mice embryos on d 13 and 14 induces massive death of migrating and mitotic cells in populations responsible for forming deep cortical layers. By the end of prenatal period either lack or insufficient development of layers V and VI was observed manifested in significant decline of cell number, spacing out and loss of neurons in certain regions. In embryos irradiated within these terms upper layers of cortex may form, although density of cell distribution in them is lower than in control.

Animals↗

[Cells-chandeliers and axo-axonal inhibition in the neocortex, hippocampus, and the dentate gyrus].

An exceptional category of cortical non pyramidal interneurons--chandelier cells or axo-axonal cells or axo-axonal cells exert specific inhibition at the level of initial segment of pyramid axons. There are evidences that chandelier cells are directly involved in the development of Alzheimer disease, a degenerative brain pathology. Morphological features and neurochemical specialization, history of opening of chandelier cells was described as well as their links in neocortex, hippocampus and dentate fascia of man and animals. Basing on results of the authors study and the findings available in literature modern conceptions on histophysiology of axo-axonal inhibition were critically analysed. It was emphasized that the function of chandelier cells is highly specified--they prevent occasional cell connections and serve as a factor of nervous system regulation.

Animals↗

[A case of medial temporal lobe epilepsy associated with occult focal cortical dysplasia in the lateral temporal neocortex].

A 29-year-old male with medial temporal lobe epilepsy(MTLE) was revealed to have "occult" focal cortical dysplasia(FCD) in the lateral temporal neocortex. He had no history of febrile convulsion and developed complex partial seizure at the age of 14 year, which became intractable. Although MRI failed to reveal structural abnormality in the temporal lobe, even retrospectively, the findings of non-invasive preoperative examination, such as video-EEG monitoring and interictal ECD-SPECT and FDG-PET, were consistent with those of the left MTLE. Intraoperative electrocorticography(ECoG) demonstrated almost continuous paroxysmal activities on the anterior part of the inferior temporal gyrus(ITG). Anterior temporal lobectomy(ATL) with hippocampectomy was performed. Histological examination revealed FCD in the small area with 0.8 mm in diameter of the resected ITG. In the ATL without preoperative invasive examination such as chronic subdural electrode recording, intraoperative ECoG recording is mandatory.

Adult↗

[Structure of the insular area in the rat cerebral neocortex].

The cytoarchitectonics of brain insular area was studied in albino rat. It was found that this part of neocortex is subdivided into two subareas, each consisting of two fields. The peculiar features of cytoarchitectonics of these subareas and fields are presented. A topographic map is suggested, describing their position on the lateral surface of cerebral hemisphere. Classification of insular area subdivisions, suggested in the present study, is discussed in connection with the data of other authors.

Animals↗

Global gene expression analysis of developing neocortex using SAGE.

The mammalian brain is estimated to contain about a hundred billion neurons, making it the most complex biological structure on earth. Trying to understand the assembly and function of this elaborate organ is a formidable task. Yet the information to build a brain is encoded by no more than a subset of the 80,000 genes present in the genome, a more manageable number. This review describes the use of SAGE technology (Serial Analysis of Gene Expression) to decode the genetic repertoire of genes that are differentially expressed in time and in space during development of the neocortex, the part of the mammalian brain responsible for complex traits. We demonstrate that SAGE is not only powerful for generating comprehensive molecular portraits from the developing cortex but can also assist in discovering new genes.

Animals↗

[Dependence of different spike sequences on the mean neuronal firing rate in the neocortex in vivo and in vitro].

Neuronal spikes were recorded extracellularly in rabbit visual cortex in vivo (88 cells) and in surviving slices of guinea pig sensorimotor cortex in vitro (50 cells). Spike sequences (SS) with monotonically increasing (SS+) and decreasing (SS-) interspike intervals were detected. Relative number of spikes of SS in the recording was closely associated with SS generation. The relative number of spikes was plotted against the average firing rate, this function had a biphasic character with the critical point around 7 Hz. The rate of change in interspike duration (the slope) was virtually independent of the firing rate, but was significantly different in vivo and in vitro conditions for both SS+ (325 and 180 ms/s, respectively) and SS- (270 and 160 ms/s, respectively). By and large, in vivo and in vitro the spike sequence parameters depended in the average firing rate in the same manner. The role of the spike sequences in rhythmic and information processes in neocortex is discussed.

Action Potentials↗

Functional autaptic neurotransmission in fast-spiking interneurons: a novel form of feedback inhibition in the neocortex.

Autapses are synapses made by a neuron onto itself. Although morphological evidence for existence of autapses has been reported in several brain areas, it is not known whether such self-innervation in the neocortex is functional and robust. Here we report that GABAergic autaptic activity is present in fast-spiking, but not in low-threshold spiking, interneurons of layer V in neocortical slices. Recordings made with the perforated-patch technique, in which physiological intracellular chloride homeostasis was unperturbed, demonstrated that autaptic activity has significant inhibitory effects on repetitive firing and increased the current threshold for evoking action potentials. These results show that autapses are not rudimentary nonfunctional structures, but rather they provide a novel and powerful form of feedback inhibitory synaptic transmission in one class of cortical interneurons.

Action Potentials↗

Submillisecond synchronization of fast electrical oscillations in neocortex.

Fast electrical oscillations (FOs; >200 Hz) in the sensory neocortex can be recorded in a variety of species, including humans, and may reflect extremely fast integration of sensory information. This report demonstrates that, in the whisker representation of rat cortex, multivibrissa stimulation produces propagating FO field potential patterns and time-locked unit activity that are sensitive to submillisecond delays in interstimulus intervals. We propose that FOs may be produced by synchronized population spikes and their subthreshold sequelas in cortical pyramidal cells. FOs serve to accurately mark stimulus onset as a phase-encoded excitatory signal, producing phase-sensitive interactions that, in the context of exploratory whisking, may extract features of an object under exploration.

Action Potentials↗