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PubMed1988

Effects of the unilateral striatal lesion on neurotransmitter markers in the contralateral striatum and both substantia nigrae of the rat.

We investigated quantitative changes in possible neurotransmitters and their biosynthetic enzymes in the contralateral striatum and both substantia nigrae following unilateral electrothermic lesions of the striatum in the rat. Two types of changes were observed: (1) the first ones were long-lasting (up to 56 post-operative days) effects and consisted in a decrease of GABA content and tyrosine hydroxylase activity in the ipsilateral substantia nigra due to the anterograde and retrograde degeneration of striatal efferent and afferent fibres, respectively, and in a marked increase of glutamate and GABA contents in the contralateral striatum resulting possibly from a modified activity of the collaterals of the glutamatergic corticostriatal fibres and a subsequent secondary increase of GABA. The latter interpretation was supported by the finding that the changes observed were abolished by an additional callosal transection; (2) the second series of changes were transient (only found at 3-7 post-operative days) effects represented by an increase in GABA content, a decrease of tyrosine hydroxylase activity, and a decrease of dopamine content, which mostly appeared in the contralateral substantia nigra. The decrease of dopamine markers may be a subsequent secondary effect of the increase of GABA in the substantia nigra. These results suggest that the contralateral increase of the amino acid transmitters in the striatum and the increase followed by decrease of transmitter markers in the contralateral substantia nigra could be a "plastic" or "compensatory" biochemical response to the unilateral striatal lesions.

Animals↗
PubMed1989

Intracellular lucifer yellow injection in fixed brain slices combined with retrograde tracing, light and electron microscopy.

The present paper contains a full methodological description of iontophoretic Lucifer Yellow injections in fixed brain slices in mammals. In brief, cortical tissue was either perfused or immersion-fixed in paraformaldehyde. After Vibratome sectioning, tissue slices were transferred to epifluorescence microscopes equipped with long distance objectives. Under visual guidance, neurons were selectively impaled with Lucifer Yellow-filled electrodes and intracellularly injected until all dendrites appeared brightly fluorescent. Excellent dendritic staining was obtained in both perfusion-fixed cat visual cortex and immersion-fixed human brain biopsies. Dendritic spines, varicosities and growth cones could be readily discerned. Filling of axonal collaterals was, however, incomplete. Callosally projecting neurons in cat visual cortex were retrogradely traced with a mixture of the fluorescent tracers Fast Blue and DiI. Subsequently the morphology of labelled cells was determined by intracellular Lucifer Yellow injection. Although the Fast Blue fluorescence had become undetectable in filled neurons the granular red appearance of DiI was still discernible. Hence the neuronal composition of even relatively sparse projections can be demonstrated. To obtain permanent preparations, dye-filled neurons were immersed in a diaminobenzidine solution and irradiated with epifluorescent illumination until all visible fluorescence had faded. Photo-oxidation resulted in the intracellular formation of a homogeneously distributed brown reaction product visible with the light microscope. Brief osmication enhanced the staining contrast, thus providing a Golgi-like image. Subsequent electron microscopy of photo-converted cells showed the fine granular nature of the electron opaque reaction product, thus revealing numerous cytological features. The precipitate was homogeneously distributed throughout the entire cytoplasm and nucleus, extending into dendrites and axon. Any apparent leakage of the label into the extracellular space was not observed. Intracellular staining in fixed tissue yields a high number of neurons with extensive filling of dendritic arbors. Photo-oxidation provides stable, non-fading preparations with the option of subsequent electron microscopy. In addition, the technique can be combined with immunocytochemistry and a variety of fluorescent tracer substances. These features, combined with its high selectivity and relative methodological simplicity, render the method to be a promising alternative to classical neuroanatomical approaches.

Animals↗
PubMed1994

Ipsilateral motor control of the forelimb in the congenitally acallosal mouse.

The corticospinal projections of mice with callosal agenesis were investigated using electro-physiological and horseradish peroxidase techniques. In the normal mouse, intracortical stimulation of the motor area with the microelectrode resulted in contralateral contraction of the forelimb, whereas ipsilateral contraction was observed in the acallosal mouse. Hence, mice with congenital absence of the corpus callosum show physiologically ipsilateral motor control. Furthermore, latency of the forelimb contraction elicited by electrical stimulation of the acallosal mouse was slightly shorter than that of the normal mouse. On the other hand, it was confirmed by a horseradish peroxidase technique that the corticospinal tract and peripheral motor neurons in the spinal cord of the acallosal mouse were identical to those of the normal mouse.

Agenesis of Corpus Callosum↗
PubMed1983

Schizophrenia, abnormal connection, and brain evolution.

Abnormalities of functional connection between specialized areas in the human brain may underlie the symptoms which constitute the schizophrenia syndrome. Callosal and intrahemispheric fibres may be equally involved. The clinical emergence of symptoms in the later stages of brain maturation may be dependent on myelination of these fibre groups, both of which have extended myelination cycles. Ontogenetically earlier variants of the same mechanism could theoretically result in dyslexia and the syndromes of Kanner and Gilles de la Tourette. As new and unique extensions of specialized function emerge within the evolving brain, biological trial and error of connection both within and between them may produce individuals possessing phylogenetically advanced abilities, or equally, others possessing a wide range of abnormalities including those which comprise the schizophrenia syndrome. A dormant phenotypic potential for schizophrenia may exist in individuals who never develop symptoms during the course of a lifetime though some of these may become clinically apparent under the influence of various precipitating factors. It is concluded that abnormal functional connection and its normal and "supernormal" counterparts may be natural, essential, and inevitable consequences of brain evolution, and that this may have been so throughout the history of vertebrate brain evolution.

Agenesis of Corpus Callosum↗
PubMed1991

Bicuculline-induced neocortical epileptiform foci and the effects of 6-hydroxydopamine in developing rats.

Catecholamines (dopamine and norepinephrine) are considered to be predominantly inhibitory neurotransmitters in the brain and their depletion produced by 6-hydroxydopamine may result in proconvulsant effects. In our experiments on rats aged 5, 7, 9, 12, 15, 18, 25 and 90 days under urethane anesthesia we demonstrated the development of neocortical epileptic focus evoked by topical application of bicuculline methiodide. In experimental groups aged 7, 12, 18, 25 and 90 days a chronic depletion of catecholamines was induced using pretreatment with 6-hydroxydopamine early postnatally. An epileptogenic focus was induced in all age groups; duration of a single discharge decreased with age in both control and experimental animals. The spread of activity from the primary focus to contralateral frontal cortex via callosal connections was as rapid as in controls. However, the transfer of discharge to occipital regions was delayed and the number of discharges decreased in experimental rats. Our study demonstrated a substantial role of catecholamines for synchronization of focal discharges in neocortex and a promoting role of catecholamines in association pathways within neocortex.

Animals↗
PubMed1988

Layer V in rat auditory cortex: projections to the inferior colliculus and contralateral cortex.

This study compares the form and distribution within layer V of cells projecting to the inferior colliculus with that of commissural cells of origin in adult rat auditory cortex after horseradish peroxidase injections in the ipsilateral inferior colliculus or auditory cortex. The goal of this work was to determine whether every part of layer V participates equally in both projections, and if the cortical neurons in each pathway were similar. The types of neurons were defined in Golgi-Cox preparations and matched with the profiles of retrogradely labeled cells from architectonically defined cortical area 41. Inferior colliculus and commissural neurons form two populations that differ in their distribution in layer V, in somatic area, and in the form of their apical dendritic arbors. Corticocollicular neurons include the largest pyramidal cells, whose robustly filled apical dendrites ascend into layer II or farther. Commissural cells are smaller and have a more heterogeneous form. Their apical dendrites do not usually extend above layer IV, and a few of these cells may be non-pyramidal. Small pyramidal cells and inverted pyramidal cells project to the opposite cortex, but not to the inferior colliculus. Medium-sized pyramidal cells project in both systems. In addition, certain callosal cells of origin in layers V and III were morphologically similar. More than one-third of the commissural cells originate in the superficial part of layer V, where only 7% of the inferior colliculus projection neurons arise. Most corticocollicular cells lie deeper in layer V, where there are fewer commissural neurons. These findings suggest that the efferent systems projecting to telencephalic and mesencephalic targets are morphologically distinct and spatially segregated in layer V. However, the commissural projection includes similar cells in different cortical layers. The types of these efferent neurons may be more closely related to their target than to their laminar origin.

Animals↗
PubMedDate not supplied

An MRI study of the myelination pattern in West syndrome.

Using magnetic resonance imaging (MRI), we studied the myelination of the brains of 8 patients with West syndrome. All cases were symptomatic, 2 having severe asphyxia, 1 lissencephaly, 1 Leigh encephalopathy, 2 tuberous sclerosis, 1 multiple anomalies and 1 microcephaly. Myelination of the pons, cerebellum, thalamus, internal capsules, optic radiation, centrum semiovale and cerebral white matter was separately assessed. The 2 cases with tuberous sclerosis exhibited normal myelination patterns, although asymmetry of the cerebral white matter was noted. These cases had a moderate degree of mental retardation and persistent seizures. The other 6 cases exhibited a marked delay of myelination throughout the central nervous system except for the midbrain. These cases had severe psychomotor retardation and persistent seizures. Although the difference in the outcome may simply reflect the different etiological disorders, these results suggest that the myelination pattern is related to the psychomotor retardation but not to the severity of the seizures in West syndrome. Atrophy of the corpus callosum developed during ACTH therapy and disappeared after the therapy. It was thus suggested that the callosal atrophy caused by the ACTH therapy was reversible.

Atrophy↗
PubMed1996

Effects of cocaine on the rat cerebral commissure.

We investigated the effects of cocaine on the corpus callosum, the nerve fibre bundle that connects the bilateral cerebral hemispheres. Our experiments in rats confirmed that, in the control group, the mid-sagittal area of the corpus callosum in the adult male was significantly larger than this area in the female. Early postnatal exposure to cocaine abolished this sexual dimorphism, that is, cocaine-treated males had a significantly smaller callosal area than the control males. Cocaine induced no significant changes in the weight of the body or brain. There were no significant sex differences in the midline sagittal area of the anterior commissure, and no apparent effects of cocaine exposure were determined in this structure. These findings suggest that early postnatal exposure to cocaine abolishes the sexual differentiation of the corpus callosum in male rats.

Animals↗
PubMed1987

The mouse neocortical slice: preparation and responses to excitatory amino acids.

1. An improved method of preparing wedges of cerebral cortex and corpus callosum from 500 microM thick coronal sections using mouse brain is described. 2. The characteristics of mixing in the two compartment baths is fully reported. 3. Cortical tissue could be depolarized relative to callosal tissue by superfusion of N-methyl-D-aspartate (NMDA), quinolinate, kainate or quisqualate. 4. At higher concentrations of agonists the depolarization was followed by a small hyperpolarization. This hyperpolarization was abolished by 5 microM ouabain. 5. Neither TTX (1 microM) nor bicuculline (50-62.5 microM) significantly affected the amplitude of the responses to the excitatory amino acids. 6. Responses to NMDA and quinolinate were selectively reduced by magnesium ions, 2-amino-5-phosphonovalerate or ketamine.

Amino Acids↗
PubMedDate not supplied

Effects of postnatal exposure to cocaine on the development of the rat corpus callosum.

We investigated the effects of cocaine on the development of the corpus callosum in rats. From postnatal days 1 (P1) to 10 (birth = P0), cocaine (10 mg/kg) was subcutaneously injected in the pups, and saline, at the same volume, was administered to control pups. The animals were sacrificed at 110 days of age and a midsagittal section of the callosum was obtained. Morphometric measurement of the corpus callosum was performed in this section. In the control group, but not in the cocaine group, males had larger callosa than females. The cocaine treatment significantly decreased the total callosal area in male rats. These findings indicate that early postnatal cocaine abolishes the sexual differentiation of the corpus callosum.

Analysis of Variance↗
PubMedDate not supplied

Absence of the septum pellucidum and related disorders.

We present an illustration of the spectrum of intracranial abnormalities associated with absence of the septum pellucidum to better define and illustrate this disorder. CT and 1.5 Tesla MRI examinations of fifteen patients with absence of the septum pellucidum were meticulously analyzed and correlated with clinical and laboratory studies. The findings were compiled and categorized based upon the presence and type of associated radiologic abnormalities. Absence of the septum pellucidum may occur as an isolated abnormality (n = 3). In most patients (n = 12), associated complex developmental abnormalities are present which include heterotopias, hypoplastic falx, ventricular clefts, encephalocele, small pituitary gland, small optic nerves and chiasm, and corpus callosal dysgenesis. Inferior pointing and a squared-off appearance of the frontal horns are frequently noted. These, or other, more severe ventricular configuration deformities are present in all patients. We have portrayed the complete range of findings associated with absence of the septum pellucidum using an illustrative approach to clarify the different patterns of radiologic abnormalities which may be seen with this complex entity.

Adolescent↗
PubMed1991

Differential expression of voltage-gated calcium channels in identified visual cortical neurons.

Using the whole-cell patch-clamp technique, Ca2+ channel currents were examined in three distinct types of neurons derived from rat primary visual cortex. Callosal-projecting and superior colliculus-projecting neurons were identified following in vivo retrograde labeling with fluorescent "beads." A subset of intrinsic GABAergic visual cortical neurons was identified with the monoclonal antibody VC1.1. Although high voltage-activated Ca2+ channel currents were measured in all three cell types, clear differences in the densities of these channels were observed. There were also marked variations in the relative amplitudes of the inactivating and noninactivating components of the high voltage-activated currents, suggesting that N- and L-type Ca2+ channels are differentially distributed. Although low voltage-activated or T-type currents were measured in subsets of both types of projection neurons, they were not observed in VC1.1-positive cells. These results provide a direct demonstration that voltage-gated Ca2+ channels are expressed in neurons of the mammalian visual cortex and reveal that the distribution and densities of different Ca2+ channel types in diverse classes of visual cortical neurons are distinct.

Animals↗
PubMedDate not supplied

A study of the corpus callosum in epilepsy using magnetic resonance imaging.

The corpus callosum of a group of epileptic patients (N = 48) was compared to that of normal healthy volunteers (N = 14) using magnetic resonance imaging (MRI). The mid-callosal thickness was significantly greater in the sub-group of epileptic patients with generalized seizures. This provides some support for the concept of the corpus callosum playing a role in seizure propagation.

Adolescent↗
PubMedDate not supplied

Interhemispheric desynchronization of spontaneous spike-wave discharges by corpus callosum transection in rats with petit mal-like epilepsy.

Wistar rats of a strain inbred for spontaneous generalized non-convulsive seizures present EEG spike-wave discharges (SWDs), 7-10 c/sec, occurring about once/min and lasting about 15 sec. They are bilateral and synchronous and can be recorded over the entire neocortex and in the lateral thalamic nuclei. After corpus callosum section, only a few bilateral SWDs persisted. Asymmetrical SWDs were most often recorded: bilateral SWDs starting asynchronously, or unilateral SWDs, which were also seen to alternate abruptly between hemispheres. The thalamic SWDs were always synchronized with the ipsilateral cortical pattern. These findings suggest that while the corpus callosum has a major role in bilateral synchronization of SWD in this model of epilepsy, occasional synchronization may still occur through other pathways after callosal transection.

Animals↗
PubMed1993

Size of the corpus callosum and auditory comprehension in schizophrenics and normal controls.

19 schizophrenic patients and 15 normal controls, matched for sex and age, were evaluated by magnetic resonance imaging for corpus callosal size and had neuropsychological functioning assessed using an auditory comprehension test. Although the MRI data did not reveal any significant differences between groups, the degree of laterality to the left versus right ear response was significantly correlated with the size of the posterior part of the corpus callosum in male schizophrenics.

Adult↗
PubMed1993

Frontal lobe metabolism and cerebral morphology in schizophrenia: 31P MRS and MRI studies.

The relation between frontal lobe membrane phospholipid metabolism as measured by 31Phosphorus magnetic resonance spectroscopy (31P MRS) and cerebral morphology as measured on magnetic resonance images (MRI) was examined in nine first episode neuroleptic naive schizophrenic patients. Total corpus callosal area was significantly correlated with phosphodiester concentration. When examined separately, this relation was confined to the rostral quartile (genu) of the corpus callosum. The pathophysiological significance of this finding is discussed in relation to neurodevelopmental hypotheses of schizophrenia.

Adult↗
PubMed1994

Brain structure changes in schizophrenics with high serum titers of antibodies to herpes virus.

We compared five indices of brain structure between two groups of schizophrenics, namely, those with high and normal levels of antibody in the serum to herpes virus. Eleven 'immuno-positive' and 21 'immuno-normal' subjects obtained from a concomitant study of serum IgG antibody to viruses underwent magnetic resonance imaging (MRI) utilizing a 1 Tesla magnet and 8 mm thick slices. We measured ventricle-brain ratio (VBR), 3rd ventricle width, cortical atrophy, area of corpus callosum, and frontal lobe area. The differences between groups were assessed by t-test and chi-square analysis. Eight of 11 immuno-positives compared to 7 of 21 immuno-normals showed evidence of cortical atrophy (chi 2 = 4.49, p < 0.03). The immuno-positives had smaller left frontal area (mean + s.d = 125.69 + 21.30 versus 143.76 + 19.84, t = 2.07, p < 0.05) and larger 2nd quadrant of the corpus callosum (mean + s.d. = 1.58 + 0.39 versus 1.27 + 0.52, t = 2.68, p < 0.01). The right frontal area also was smaller in immuno-positives but not significant. VBR, 3rd ventricle and the 1st, 3rd and 4th callosal quadrants did not differ between the groups. We conclude that high antibody titers to herpes found in the sera of some schizophrenics might reflect an earlier pathogenetic process that affected brain development. Further studies of antibodies in CSF and brain structure in these or similar subjects and those suspected to be exposed to viral infections in utero should be vigorously pursued to obtain definitive evidence for this hypothesis.

Adult↗
PubMed1995

Abnormalities in midline attentional circuitry in schizophrenia: evidence from magnetic resonance and positron emission tomography.

The syndrome of schizophrenia presents with a complex array of symptoms that are difficult to explain at the neural level. Data collected using magnetic resonance (MR) and positron emission tomography (PET) suggest that this complex array could occur as a consequence of misconnections and mismatches in midline circuitry that is reticular-thalamic-cingulate-cortical. MR studies have shown a variety of abnormalities, including callosal agenesis, cavum septi pellucidi, decreased thalamic size, decreased frontal size, and changes in signal intensity in white matter tracts between the thalamus and the frontal cortex. PET studies using a dichotic listening paradigm suggest that patients suffering from schizophrenia have brain blood flow abnormalities consistent with a difficulty in focusing or shifting attention, which may reflect the functional substrate of the anatomic abnormalities.

Attention↗