Long-range correlations in rabbit brain neural activity.

We have analyzed the presence of persistence properties in rabbit brain electrical signals by means of non-equilibrium statistical physics tools. To measure long-memory properties of these experimental signals, we have first determined whether the data are fractional Gaussian noise (fGn) or fractional Brownian motion (fBm) by calculating the slope of the power spectral density plot of the series. The results show that the series correspond to fBm. Then, the data were studied by means of the bridge detrended scaled windowed variance analysis, detecting long-term correlation. Three different types of experimental signals have been studied: neural basal activity without stimulation, the response induced by a single flash light stimulus and the average of the activity evoked by 200 flash light stimulations. Analysis of the series revealed the existence of persistent behavior in all cases. Moreover, the results also exhibited an increasing correlation in the level of long-term memory from recordings without stimulation, to one sweep recording or 200 sweeps averaged recordings. Thus, brain neural electrical activity is affected not only by its most recent states, but also by previous states much more distant in the past.

Excitotoxic insults to the optic nerve alter visual evoked potentials.

Excitotoxic oligodendroglial death is one of the mechanisms which has been proposed to underlie demyelinating diseases of the CNS. We describe here functional consequences of excitotoxic lesions to the rabbit optic nerve by studying the visual evoked potentials (VEPs) measured in the visual cortex. Nerves were slowly infused with the excitotoxin kainate a subcutaneously implanted osmotic pump which delivered the toxin through a cannula onto the optic nerve. Records of VEPs were obtained before pump implantation and at 1, 3 and 7 days post-implantation, and weekly evaluated thereafter for up to 4 months. We observed that the VEPs generated by light stimuli progressively changed in both amplitude and profile after the lesion as well as in comparison to those generated in control animals infused with vehicle. Histological examination of the damage caused by the excitotoxic insult showed that large areas of the optic nerve were demyelinated and their axons distorted. These observations were confirmed and extended by immunohistochemical analyses using markers to neurofilaments, myelin basic protein and the oligodendrocyte marker APC. The results of the present paper indicate that the consequences of excitotoxicity in the optic nerve share functional and morphological alterations which are found in demyelinating disorders. In addition, this experimental paradigm may be useful to evaluate the functional recovery of demyelinated optic nerves following various repair strategies.

The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down-regulated by the antipsychotic drug clozapine.

We show here that clozapine, a beneficial antipsychotic, down-regulates the expression of the glutamate transporter GLT-1 in the rat cerebral cortex, thereby reducing glutamate transport and raising extracellular glutamate levels. Clozapine treatment (25--35 mg kg(-1) day(-1) orally) reduced GLT-1 immunoreactivity in several brain regions after 3 weeks; this effect was most prominent after 9 weeks and most evident in the frontal cortex. GLT-1 protein levels were reduced in the cerebral cortex of treated rats compared with controls and were more severely affected in the anterior (71.9 +/- 4.5%) than in the posterior (53.2 +/- 15.4%) cortex. L-[(3)H]-glutamate uptake in Xenopus laevis oocytes injected with mRNA extracted from the anterior cerebral cortex of rats treated for 9 weeks was remarkably reduced (to 30.6 +/- 8.6%) as compared to controls. In addition, electrophysiological recordings from oocytes following application of glutamate revealed a strong reduction in glutamate uptake currents (46.3 +/- 10.2%) as compared to controls. Finally, clozapine treatment led to increases in both the mean basal (8.1 +/- 0.7 microM) and the KCl-evoked (28.7 +/- 7.7 microM) output of glutamate that were 3.1 and 3.5, respectively, higher than in control rats. These findings indicate that clozapine may potentiate glutamatergic synaptic transmission by regulating glutamate transport.

The link between excitotoxic oligodendroglial death and demyelinating diseases.

Oligodendrocytes, the myelinating cells of CNS axons, are highly vulnerable to excitotoxic signals mediated by glutamate receptors of the AMPA and kainate classes. Receptors in these cells are commonly activated by glutamate that is released from axons and glial cells. In addition, oligodendrocytes contribute to the control of extracellular glutamate levels by means of their own transporters. However, acute and chronic alterations in glutamate homeostasis can result in overactivation of AMPA and kainate receptors and subsequent excitotoxic oligodendroglial death. Furthermore, demyelinating lesions caused by excitotoxins can be similar to those observed in multiple sclerosis. This, together with the effect of AMPA and kainate receptor antagonists in ameliorating the neurological score of animals with experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis), indicates that oligodendrocyte excitotoxicity could be involved in the pathogenesis of demyelinating disorders.

Activation of volume-regulated Cl(-) channels by ACh and ATP in Xenopus follicles.

Osmolarity-dependent ionic currents from follicle-enclosed Xenopus oocytes (follicles) were studied using electrophysiological techniques. Whole follicle currents were monitored using a two-electrode voltage clamp and single-channel activity was measured using the patch-clamp technique. In follicles held at -60 mV two chloride currents were activated in external hyposmotic solutions. One was the habitual volume-regulated current elicited by external hyposmolarity (ICl,swell), and the second was a slow and smooth current (Sin) generated by ACh or ATP application. In follicles, the permeability ratios for different anions with respect to Cl- were similar for both ICl,swell and Sin, with a sequence of: SCN- > I- > Br- >= NO3- >= Cl- > gluconate >= cyclamate > acetate > SO42-. Extracellular ATP blocked the outward component of Sin. Also, extracellular pH modulated the inactivation kinetics of Sin elicited by ACh; e.g. inactivation at +80 mV was approximately 100 % slower at pH 8.0 compared with that at pH 6.0. Lanthanides inhibited ICl, swell and Sin. La3+ completely inhibited ICl,swell with a half-maximal inhibitory concentration (IC50) of 17 +/- 1.9 microM, while Sin was blocked up to 55 % with an apparent IC50 of 36 +/- 2.6 microM. Patch-clamp recordings in follicular cells showed that hyposmotic challenge opened inward single-channel currents. The single channel conductance (4.7 +/- 0.4 pS) had a linear current-voltage relationship with a reversal membrane potential close to -20 mV. This single-channel activity was increased by application of ACh or ATP. The ICl,swell generation was not affected by pirenzepine or metoctramine, and did not affect the purinergic activation of the chloride current named Fin. Thus, ICl,swell was not generated via neurotransmitters released during cellular swelling. All together, equal discrimination for different anions, similar modulatory effects by extracellular pH, the blocking effects by ATP and La3+, and the same single-channel activity, strongly suggest that ICl,swell and Sin currents depend on the opening of the same type or a closely related class of volume-regulated chloride channels.

Morphology of neurons in the superficial layers of the rabbit's superior colliculus projecting ipsilaterally to the pons.

The superior colliculus (SC) is a laminar structure which can be separated into superficial and deep layers according to morphological and functional criteria. The superficial layers are interconnected with many nuclei, most of which process visual information. Also, these layers are known to project to the pontine grey. The topography of the projection is well established in many mammals but little is known about the morphology of the cells of origin of the projection. The pons of two adult albino rabbits were injected with Rhodamine latex microspheres and the retrogradely labeled cells in the SC were intracellularly filled with Lucifer yellow. The distribution of the labeled cells was organized into two bands. The upper one (71% of the cells) was located in the middle third of the stratum griseum superficiale (SGS). The lower band was less dense (29% of the cells) and located in the lower third of SGS and in the upper layers of the stratum opticum. Neurons corresponding to the upper band were preferentially vertically oriented. In particular, 47% were vertical fusiform, 23.5% globular/pyriform, 17.7% horizontal and 11.8% stellate in their morphology. Neurons corresponding to the lower band did not present so clear polarization. Thus, 57.1% were stellate, 28.6% were horizontal and 14.3% globular/pyriform. On the basis of their morphology, we consider that the cells of origin of the tectopontine projection form a particular population in the SC.

Morphological characteristics of neurons in the superficial layers of the rabbit's superior colliculus projecting to the ipsilateral dorsal lateral geniculate nucleus.

The mammalian superior colliculus (SC) may be divided into distinct layers on the basis of cytoarchitectonic criteria. These layers have different functions and patterns of connectivity. The superficial layers (stratum zonale, stratum griseum superficiale (SGS) and stratum opticum) are intimately associated with the processing of visual information. In the present study, we have investigated the morphology of the SC neurons that project ipsilaterally to the dorsal lateral geniculate nucleus (dLGN). Rhodamine latex microspheres were injected into the dLGN of nine adult rabbits. Retrogradely labeled cells were then intracellularly injected with Lucifer Yellow. The somata of the cells from which the projection originated were primarily located in a band occupying the medial third of the SGS and were found to reside at an average depth of 373 microns. Morphological analysis of these neurons revealed that 37% had a stellate shape, 27% were vertical fusiform, 18% were globular/pyriform, 14% were oriented horizontally and 4% were pyramidal in their morphology. Within each morphological class, we have examined the different subtypes with respect to incidence, localisation and characteristics of the dendritic arborizations.

Morphological characteristics of neurons in the superficial layers of the rabbit's superior colliculus projecting to the contralateral dorsal lateral geniculate nucleus.

The neuronal projection between the superficial layers of the mammalian superior colliculus (SC) and the ipsilateral dorsal lateral geniculate nucleus (dLGN) is well established. However, the participation of the contralateral SC remains controversial. In this study we have presented evidence for the existence of SC neurons which project to the contralateral dLGN and also performed a detailed statistical analysis of such SC cells. The dLGN of nine adult rabbits was injected with Rhodamine latex microspheres and the retrogradely labeled cells of the SC were intracellularly injected with Lucifer yellow. The number of labeled cells is less than that found in the ipsilateral SC, but some are always present. The somata of these cells are located mainly in the lower half of the stratum griseum superficiale at a mean depth of 738 microns. 40% of the cells were horizontal, 34% stellate, 23% globular or pyriform and 3% vertical fusiform in their morphology. On the basis of morphology and localization, this population is clearly distinct from the corresponding ipsilateral cell population.

Morphology of visual cortical neurons projecting to the pons. A study with intracellular injection of lucifer yellow in the cat.

The aim of this study is to describe the morphological features of the origin cells of the visual corticopontine projection in the cat. To this end, the pontine grey matter of adult cats was injected with Rhodamine Latex Microspheres. The resulting, retrogradely marked cells of the visual cortex, were subsequently injected intracellularly with Lucifer Yellow. The majority of these cells (68%) were layer V pyramidal cells. However, a significant proportion of these retrogradely-labeled cells were atypical (26.5%) and non-pyramidal (5.5%) in their morphology. The majority of the labeled cells were found at the interhemispheric surface. The somatic dimensions of the visual corticopontine cells were on average 22.8 x 17.0 microns. The mean number of basal dendrites of pyramidal cells was 5.3 and their average tangential spread was 296.1 microns. For non-pyramidal cells, the values were 3.2 and 195.6 microns respectively. The main bifurcation of apical dendrites was located on average at 95.0 microns from the soma and their mean tangential spread was 193.9 microns. The depth of the soma was on average 1086.9 microns from the pial surface.

Distribution of cortico-visual neurons projecting to the pons in the cat. A retrograde labelling study with rhodamine latex microspheres.

Injections of the low diffusion retrograde tracer rhodamine latex microspheres were made in the pontine grey matter of the cat in order to study the cortical convergence to the pons. We found a different distribution of cells in the convex surface of the brain hemisphere making ventral or dorsolateral injections. In the first case, cells were grouped in the top of the gyri. In the second case, cells were more frequent in the bottom of the sulci. Our results show a possible retinotopic organization of this projection.

An easy method for impaling cells using the micromanipulation technique.

In the method described, the head of a fixed-stage microscope and the attached micromanipulator are simultaneously displaced during focussing movements of the microscope. This design allows axial displacements of the microscope towards the cell to be injected. This arrangement makes the filling of neurons in brain slices by intracellular iontophoresis injection of Lucifer yellow considerably easier.