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At least 649 records · Page 36Linked to original sources
PubMed2002

AMPA receptor activation induces GABA release from neurons migrating tangentially in the intermediate zone of embryonic rat neocortex.

In the intermediate zone of the embryonic rodent neocortex, neurons migrating tangentially from the basal ganglia express both functional amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and gamma-aminobutyric acid (GABA). To test the hypothesis of GABA release triggered by AMPA receptor activation, we used whole-hemisphere cultures prepared from rat embryos (day 15). We observed a marked decrease in the number of detectable GABA-positive cells in the intermediate zone after exposure to T-AMPA. This effect was blocked by coapplying GYKI 53655, an AMPA receptor antagonist. The decrease in GABA immunolabelling induced by T-AMPA did not require extracellular calcium. In contrast, it was abolished after sodium substitution by choline, or after coapplication of nipecotic acid, a GABA transporter inhibitor. Exposure to high potassium reduced the number of detectable GABA-positive cells. These results are compatible with carrier-mediated GABA release consecutive to sodium influx. GABA released from neurons migrating tangentially in the intermediate zone after AMPA receptor activation may influence neighbouring elements including radially migrating postmitotic neurons, proliferating progenitors and possibly the tangential cells themselves.

Animals↗
PubMed2003

Stimulation site determines the conditioned effects of kindling in rats: anterior neocortex versus amygdala.

Rats received 53 stimulations to either the left basolateral amygdala (BA) or left anterior neocortex (AN) in one environment (CS+) and 53 sham stimulations (the stimulation lead was attached but no current was delivered) in another environment (CS-), quasirandomly over 54 days. Confirming a previous report [Barnes, S.J., Pinel, J.P., Francis, L.H. & Wig, G.S. (2001) Behav. Neurosci., 115, 1065-1072], as BA kindling progressed, the CS+ began to elicit more defensive behaviours (i.e. less activity, more freezing and avoidance of the CS+) than the CS-, and at the end of the experiment, convulsions elicited in the CS+ were more severe than those elicited in the CS-. Like BA kindling, AN kindling led to less activity in the CS+; but unlike BA kindling, AN kindling led to more wet-dog-shakes and less, rather than more, severe convulsions in the CS+. During AN kindling, the mean number of wet-dog-shakes in the CS+ was negatively correlated with the mean convulsion class, suggesting that wet-dog-shakes contribute to the inherent variability of AN kindling. These findings confirm that inherent conditioned effects influence kindled convulsions and interictal behaviour and establish for the first time that the pattern of these conditioned effects is a function of the kindling site.

Amygdala↗
PubMed2003

Involvement of post-synaptic kainate receptors during synaptic transmission between unitary connections in rat neocortex.

The properties of functional kainate receptor-mediated EPSCs were studied in acute slices from 19-35-day-old rats. EPSCs elicited in pyramidal and fast-spiking cells in layers 2/3 and 5 of the rat motor cortex by extracellular single shock stimulus in the presence of GYKI 53655 and D-2-amino-5-phosphopentanoic resulted in a residual current. This current was not enhanced by cyclothiazide but was blocked by 6-cyano-7-nitroquinoxalin-2,3-dione and is thought to be mediated by kainate receptors. These kainate receptor-mediated currents displayed a wide range of time courses depending on which pre-synaptic fibres were activated. With paired recordings, unitary EPSCs elicited in pyramidal cells were almost totally blocked by GYKI 53655 and D-2-amino-5-phosphopentanoic. However, when L-transpyrrolidine-2,4-dicarboxylate (PDC), a glutamate uptake blocker, was introduced in the bath, the amplitude of kainate receptor-mediated currents, which is resistant to GYKI 53655 and D-2-amino-5-phosphopentanoic, was revealed. The rise and decay time constants of the kainate receptor-mediated currents were identical to control EPSCs. PDC was not required to reveal the kainate receptor-mediated currents elicited in fast-spiking cells which also displayed similar rise and decay time constants to the control EPSCs. Excitatory input onto pyramidal and fast-spiking cells in the neocortex mediated by kainate receptors contributed between 14 and 40% of the total control unitary EPSCs which displayed identical time courses to the AMPA receptor-mediated component of the EPSCs. Post-synaptic kainate receptors at connected pyramidal cell synapses may be located extra-synaptically.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2003

Short bursts of weak pulses break postictal inhibition in the neocortex of Wistar rats.

PURPOSE: Postictal inhibition (PI) is a decrease in excitability that follows an epileptic seizure and decreases probability of new seizure occurrence. PI may involve both increased inhibition and persisting elevated excitation. Our experiments tested whether shorter trains of weak stimuli are able to unmask this residual increase of excitability during the PI. METHODS: Four epileptic afterdischarges (ADs) were evoked by intense electrical stimulation (20 s, 8 Hz, current intensity at 5x threshold) of the neocortex in two groups (A, B) of Wistar rats. Before the first AD and during the 10-min interictal period, 8-Hz trains of four weak pulses (half of the intensity used for the AD triggering; 4P) were applied every 20 s in group B and a single pulse with similar parameters in group A. RESULTS: The number of interictal epileptiform events evoked by 4P in the group B was significantly higher than that in the group A (evoked by single pulses) except after the second AD. Epileptic events were triggered by 4P also immediately after the AD termination. CONCLUSIONS: It is apparent that weak stimulation can trigger epileptic phenomena during PI. Our results indicate that it is no longer possible to perceive PI only as persisting extreme and active inhibition. An appropriate stimulation can reveal more subtle (but important) excitatory events contributing to the functional status during the postictal period.

Animals↗
PubMed2006

Spontaneous and evoked synaptic rewiring in the neonatal neocortex.

The local microcircuitry of the neocortex is structurally a tabula rasa, with the axon of each pyramidal neuron having numerous submicrometer appositions with the dendrites of all neighboring pyramidal neurons, but is functionally highly selective, with synapses formed onto only a small proportion of these targets. This design leaves a vast potential for the microcircuit to rewire without extensive axonal or dendritic growth. To examine whether rewiring does take place, we used multineuron patch-clamp recordings on 12- to 14-day-old rat neocortical slices and studied long-term changes in synaptic connectivity within clusters of neurons. We found pyramidal neurons spontaneously connecting and disconnecting from each other and that exciting the slice with glutamate greatly increases the number of new connections established. Evoked emergence of new synaptic connections requires action potential activity and activation of metabotropic glutamate receptor 5, but not NMDA receptor or group II or group III metabotropic glutamate receptor activation. We also found that it is the weaker connections that are selectively eliminated. These results provide direct evidence for spontaneous and evoked rewiring of the neocortical microcircuitry involving entire functional multisynaptic connections. We speculate that this form of microcircuit plasticity enables an evolution of the microcircuit connectivity by natural selection as a function of experience.

Action Potentials↗
PubMed2006

Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice.

The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved in the formation and dissolution of brain edema. Cerebral edema is a major cause of morbidity and mortality in stroke. It is therefore essential to know whether the perivascular pool of AQP4 is up- or down-regulated after an ischemic insult, because such changes would determine the time course of edema formation. Here we demonstrate by quantitative immunogold cytochemistry that the ischemic striatum and neocortex show distinct patterns of AQP4 expression in the reperfusion phase after 90 min of middle cerebral artery occlusion. The striatal core displays a loss of perivascular AQP4 at 24 hr of reperfusion with no sign of subsequent recovery. The most affected part of the cortex also exhibits loss of perivascular AQP4. This loss is of magnitude similar to that of the striatal core, but it shows a partial recovery toward 72 hr of reperfusion. By freeze fracture we show that the loss of perivascular AQP4 is associated with the disappearance of the square lattices of particles that normally are distinct features of the perivascular astrocyte membrane. The cortical border zone differs from the central part of the ischemic lesion by showing no loss of perivascular AQP4 at 24 hr of reperfusion but rather a slight increase. These data indicate that the size of the AQP4 pool that controls the exchange of fluid between brain and blood during edema formation and dissolution is subject to large and region-specific changes in the reperfusion phase.

Animals↗
PubMed2006

Penetrating arterioles are a bottleneck in the perfusion of neocortex.

Penetrating arterioles bridge the mesh of communicating arterioles on the surface of cortex with the subsurface microvascular bed that feeds the underlying neural tissue. We tested the conjecture that penetrating arterioles, which are positioned to regulate the delivery of blood, are loci of severe ischemia in the event of occlusion. Focal photothrombosis was used to occlude single penetrating arterioles in rat parietal cortex, and the resultant changes in flow of red blood cells were measured with two-photon laser-scanning microscopy in individual subsurface microvessels that surround the occlusion. We observed that the average flow of red blood cells nearly stalls adjacent to the occlusion and remains within 30% of its baseline value in vessels as far as 10 branch points downstream from the occlusion. Preservation of average flow emerges 350 mum away; this length scale is consistent with the spatial distribution of penetrating arterioles. We conclude that penetrating arterioles are a bottleneck in the supply of blood to neocortex, at least to superficial layers.

Animals↗
PubMed1998

Changes in cell-cycle kinetics during the development and evolution of primate neocortex.

The evolutionary expansion of neocortical size in mammals is particularly prominent in anthropoid primates (i.e., monkeys, apes, and humans) and reflects an increased number of cortical cells, yet the developmental basis for this increase remains undefined. Cortical cell production depends on the length of the cell-division cycle of progenitor cells during neurogenesis, which previously has been measured only in smaller-brained rodents. To investigate whether cortical expansion in primates reflects modification of cell-cycle kinetics, we determined cell-cycle length during neurogenesis in the proliferative cerebral ventricular zone of fetal rhesus monkeys, by using cumulative S-phase labeling with bromodeoxyuridine. Cell-cycle durations in monkeys were as much as 5 times longer than those reported in rodents. Nonetheless, substantially more total rounds of cell division elapsed during the prolonged neurogenetic period of the monkey cortex, providing a basis for increased cell production. Moreover, unlike the progressive slowing that occurs during cortical development in rodents, cell division accelerated during neurogenesis of the enlarged cortical layers in monkeys. These findings suggest that evolutionary modification of the duration and number of progenitor cell divisions contributed to both the expansion and laminar elaboration of the primate neocortex.

Animals↗
PubMed2006

The cyclin-dependent kinase inhibitors p57 and p27 regulate neuronal migration in the developing mouse neocortex.

Neuronal precursors remain in the proliferative zone of the developing mammalian neocortex until after they have undergone neuronal differentiation and cell cycle arrest. The newborn neurons then migrate away from the proliferative zone and enter the cortical plate. The molecules that coordinate migration with neuronal differentiation have been unclear. We have proposed in this study that the cdk inhibitors p57 and p27 play a role in this coordination. We have found that p57 and p27 mRNA increase upon neuronal differentiation of neocortical neuroepithelial cells. Knockdown of p57 by RNA interference resulted in a significant delay in the migration of neurons that entered the cortical plate but did not affect neuronal differentiation. Knockdown of p27 also inhibits neuronal migration in the intermediate zone as well as in the cortical plate, as reported by others. We have also found that knockdown of p27 increases p57 mRNA levels. These results suggest that both p57 and p27 play essential roles in neuronal migration and may, in concert, coordinate the timing of neuronal differentiation, migration, and possibly cell cycle arrest in neocortical development.

Animals↗
PubMedDate not supplied

Species-specific ultrastructure of neuronal lipofuscin in hippocampus and neocortex of subhuman mammals and humans.

Lipofuscin represents an integral part of neurons and glial cells in mammals and in submammalian species. It is a special lysosomal organelle, takes part of cellular metabolism, and is a structural expression of catabolic pathways. Species-specific differences of lipofuscin indicate metabolic differences of the relevant neurons. The authors have studied the ultrastructure of neuronal lipofuscin in the hippocampus and cerebral neocortex of dogs, horses, cows, elephants, rats, mice, apes, and humans to answer the question of species-specific differences of this organelle. Paraffin sections of formalin-fixed material were investigated by hematoxylin-eosin and PAS staining, by fluorescence microscopy for autofluorescence, with a laser scanning confocal microscope and by electron microscopy. In the animals studied and in humans the lipofuscin displayed, in addition to the general trilaminar substructure, species-specific appearances. No differences were found in the lipofuscin structure between neocortical and hippocampal neurons of the separate animal species. In contrast, in humans, neurons of the hippocampus showed a particular lipofuscin structure, not only different from the neocortical one, but also with differences between CA1 and CA3/4 sectors. Interestingly, in apes a transitional situation was found with slight differences between neocortical and hippocampal lipofuscin, especially in the rhesus monkey. This peculiarity was corroborated by the distribution of special pentilaminar linear structures in the lipofuscin pigment in all animals, only sparsely in the rhesus monkey and not in humans. The results indicate that lipofuscin ultrastructure of neocortical and hippocampal neurons is species specific and that lipofuscin in the human hippocampal neurons displays structures characteristic of man differing from the neocortical neuronal lipofuscin. The neuronal lipofuscin of apes, especially of the rhesus monkey displays structures in between humans and lower mammals. Nothing is known about the functional significance of these findings. They may indicate metabolic and/or functional characteristics of the relevant neurons.

Adult↗
PubMed2006

Altered expression of alpha3-containing GABAA receptors in the neocortex of patients with focal epilepsy.

Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABA(A) receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABA(A) receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABA(A) receptor subtypes using antibodies specifically recognizing the subunits alpha1, alpha2, alpha3, beta2/3 and gamma2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the alpha-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABA(A) receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in alpha3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the alpha1 and alpha2-subunits. Reduced expression in alpha3-containing GABA(A) receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased alpha3-subunit staining. The selective reduction in alpha3-containing GABA(A) receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to alpha3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epilepsy.

Adolescent↗
PubMed2000

Glutamate, GABA and precursor amino acids in adult mouse neocortex: cellular diversity revealed by quantitative immunocytochemistry.

Glutamate is an important amino acid in the neocortex for metabolic and neurotransmitter functions. The objective of this study was to detect variations in cellular glutamate content using quantitative immunocytochemistry. We show that glutamate is present in almost all cortical cells and coexists with other amino acids such as aspartate, glutamine or gamma-aminobutyric acid (GABA). The patterns of aspartate and glutamine content suggests that there are no purely aspartatergic or glutaminergic neurons. GABAergic neurons showed variable levels of the precursors such as glutamate, glutamine and aspartate. Comparison of immunoreactive patterns between two cortical areas did not detect any statistically significant differences. The mean cellular intensity for GABA and glutamate was constant across different layers. Surprisingly, we found that GABAergic neurons could coexist with either low or high levels of glutamate, suggesting that metabolic levels of glutamate in these neurons could be variable. Alternatively, some GABA neurons may utilize both GABA and glutamate for neurotransmission. We show that when variations in amino acid content are separately mapped onto individual cells, co-registration is a useful technique for reporting heterogeneity among cortical cells.

Amino Acids↗
PubMed2001

Neural activity profiles of the neocortex and superior colliculus after bimodal sensory stimulation.

Current efforts at functional mapping of multisensory neurons are hampered by the need for both cellular-level resolution and the separate visualization of activity by different sensory cues. We have used a recently developed technique that exploits the differential time course of zif268 mRNA versus protein induction in neurons after sensory stimulation. Adult male rats were visually and acoustically deprived and then exposed to one of the following stimulation sequences: (i) no sensory stimulation; (ii) 2 h visual stimulation followed by 30 min auditory stimulation; (iii) 2 h auditory stimulation followed 30 min of visual stimulation; and (iv) 2 h compound visual and auditory stimulation. The neocortex and superior colliculus (SC) were then processed for fluorescent immunocytochemistry and in situ hybridization for staining of Zif268 protein and mRNA products. We have found that activity patterns in primary visual and auditory cortices were in accord with the sequence of the compound stimulus. We also show that SC superficial layers contained a pool of exclusively unimodal neurons, similar to that of visual cortex. Activity patterns of deep SC layers contained multimodal neurons with varying degrees of visual and auditory convergence. The deep SC layers also showed that auditory processing was largely carried out by a small, bimodal group of neurons whereas visual processing was coordinated by both a large unimodal and a small bimodal pool of neurons.

Acoustic Stimulation↗
PubMed2001

Pre- and post-mitotic events contribute to the progressive acquisition of area-specific connectional fate in the neocortex.

The adult primary motor cortex (area 6) is characterized by a stronger projection to the spinal cord than the primary somatosensory cortex (area 3). Here we have explored the progressive and regressive phenomena that determine these areal differences in the number of corticospinal neurons (CSNs). CSNs were birthdated with [(3)H]thymidine and subsequently retrogradely labeled from the spinal cord. The time window of CSN production is identical in both areas. The probability that a cohort of neuroblasts project to the spinal cord is indicated by the percentage of [(3)H]thymidine-positive neurons that can be back-labeled from the spinal cord. In the neonate this fate index is significantly higher in area 6 compared with area 3, indicating that early regionalization of cell fate contributes to areal differences in CSN number. In neonatal reeler mice, an increase in CSN number was accompanied by an increased fate index, showing that the integrity of the post-mitotic environment is required for the specification of the appropriate number of neurons expressing a given connectional phenotype. Postnatal development in reeler and normal is characterized by an area-specific elimination of CSN axons, which reduces areal differences in CSN number. These results show a progressive acquisition of CSN fate in the neocortex and indicate that both early regionalization and late environmental signals contribute to determining areal differences of connectional phenotype.

Animals↗
PubMed2002

Synaptic connections and small circuits involving excitatory and inhibitory neurons in layers 2-5 of adult rat and cat neocortex: triple intracellular recordings and biocytin labelling in vitro.

Dual and triple intracellular recordings with biocytin labelling in slices of adult neocortex explored small circuits of synaptically connected neurons. 679 paired recordings in rat and 319 in cat yielded 135 and 42 excitatory postsynaptic potentials (EPSPs) and 37 and 26 inhibitory postsynaptic potentials (IPSPs), respectively. Patterns of connectivity and synaptic properties were similar in the two species, although differences of scale and in the range of morphologies were observed. Excitatory 'forward' projections from layer 4 to 3, like those from layer 3 to 5, targeted pyramidal cells and a small proportion of interneurons, while excitatory 'back' projections from layer 3 to 4 selected interneurons, including parvalbumin immuno-positive basket cells. Layer 4 interneurons that inhibited layer 3 pyramidal cells included both basket cells and dendrite-targeting cells. Large interneurons, resembling cells previously described as large basket cells, in layers 4 and 3 (cat), with long myelinated horizontal axon collaterals received frequent excitatory inputs from both layers. A very high rate of connectivity was observed between pairs of interneurons, often with quite different morphologies, and the resultant IPSPs, like the EPSPs recorded in interneurons, were brief compared with those recorded in pyramidal and spiny stellate cells.

Animals↗
PubMed2003

Interlaminar connections in the neocortex.

This review summarizes the local circuit, interlaminar connections in adult mammalian neocortex. These were first demonstrated with anatomical techniques, which indicate some of the exquisite spatial precision present in the circuitry. Details, such as the class(es) of neurons targeted by some of these projections, have begun to be added in studies that combine paired/triple intracellular recordings with dye-filling of connected neurons. Clear patterns are emerging from these studies, with 'forward' projections from layer 4 to 3 and from 3 to 5 targeting both selected pyramidal cells and interneurons, while 'back' projections from layer 5 to 3 and from 3 to 4 target only interneurons. To place these data in a wider context, the major afferent inputs to and efferent outputs from each of the layers are discussed first.

Afferent Pathways↗
PubMed2003

Presynaptic frequency filtering in the gamma frequency band; dual intracellular recordings in slices of adult rat and cat neocortex.

Using dual intracellular recordings in slices of adult rat and cat neocortex, the frequency-filtering characteristics of 'depressing' synapses made by pyramidal axons at interspike intervals between 5 and 50 ms were studied. At 'depressing' connections from excitatory cells to some inhibitory interneurons (n = 6), recovery from short interspike interval depression was near exponential. Extrapolation of exponentials fitted to this recovery demonstrated a residual 10-20% depression at intervals >50 ms. This slowly decaying component was larger for later excitatory postsynaptic potentials (EPSPs) in trains which were typically more strongly depressed. At >80% of connections between spiny excitatory cells and at pyramid to parvalbumin-immunopositive interneuron connections, however, recovery exhibited a more complex time course. A narrow 'notch' (half-width 5 ms), peaking at intervals of 13-25 ms during which the EPSP was depressed further, interrupted recovery from short interval depression. This 'notch' was equally apparent for all EPSPs in brief trains and was mediated presynaptically.

Action Potentials↗
PubMed2003

Regional effects of wheel running and environmental enrichment on cell genesis and microglia proliferation in the adult murine neocortex.

We here report that voluntary wheel running led to a regional increase in the number of newly generated cortical microglia. We asked how adult cortical cell genesis would respond to environmental enrichment and physical activity, both stimuli that robustly induce adult hippocampal neurogenesis. After labeling proliferating cells with bromodeoxyuridine (BrdU) and immunohistochemical detection of BrdU, we found that both experimental paradigms did not result in general effects on cell proliferation and cell genesis in the neocortex. However, there were regionally and layer specific changes in the number of BrdU marked cells, both 1 day and 4 weeks after BrdU. Environmental enrichment led to a significant increase in the number of new astrocytes in layer 1 of the motor cortex. Voluntary wheel running, in contrast, caused an induction in the proliferation of microglia in superficial cortical layers of several brain regions. Under no condition was the number of new oligodendrocytes measurably enhanced. In contrast to the hippocampus, we did not find any new neurons in the cortex. The physiological 'activation' of microglia adds a new aspect to the question of microglial function in the healthy brain and of how adult brain cells can plastically react to physiological stimuli.

Animals↗