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Occipital cortical neurons with transient pyramidal tract axons extend and maintain collaterals to subcortical but not intracortical targets.

During the early postnatal development of the rat large numbers of pyramidal tract neurons are present in layer V of the occipital cortex, but by the end of the third postnatal week the distribution of pyramidal tract neurons becomes restricted to the more rostral cortical areas. This restriction is brought about by selective collateral elimination rather than by cell death. We have found, by using retrogradely transported fluorescent dyes as either short-term or long-term markers, that occipital cortical neurons which had transiently extended pyramidal tract axons maintain subcortical axonal connections to either the superior colliculus or the pons, and, at least in the case of the corticotectal projection, that the maintained collateral is present prior to the elimination of the transient pyramidal tract collateral. Further, it appears that at no time during postnatal development do the occipital pyramidal tract neurons form either callosal or ipsilateral cortico-cortical collaterals. Thus in the early postnatal occipital cortex the neurons which project through the pyramidal tract constitute a population of cells which is separate from neurons which make cortico-cortical connections, but which largely overlaps with the population of corticotectal and corticopontine neurons.

Amidines↗

Unilateral and bilateral cortical spreading depression interferes with radial maze performance in rats.

Seven rats with implanted cortical electrodes were trained in a 12-arm radial maze to asymptomatic performance (1.38 errors per trial). Single waves of cortical spreading depression (CSD) were elicited by application of cathodal current to the parieto-occipital cortex and monitored by suppression of callosal responses in the frontal cortex. Bilateral CSD elicited before the trial caused a small increase of error incidence in choices 1-6 but did not affect accuracy of choices 7-12. Bilateral CSD between choices 6 and 7 increased error incidence in the second half of the trial from 1.33 to 2.84, i.e. almost to the chance level of 3.0. Unilateral CSDs elicited before the first half of the trial in one hemisphere and in the same or in the contralateral hemisphere before the second half of the trial caused similar deterioration of performance in choices 7-12 (2.4 and 2.1 errors, respectively). It is concluded that the CSD effects have both proactive and retroactive components and that the working memory record is not lateralized at the cortical level.

Animals↗

The corpus callosum during postnatal undernourishment and recovery: a morphometric analysis of myelin and axon relationships.

This study was designed to compare morphometric relationships between myelin lamellae and axons in undernourished and well nourished developing rats, and in rats nutritionally rehabilitated for two weeks. Although sampling techniques employed in this study were not specifically designed to compare numbers of myelinated fibers in test and control populations, we did observe a trend indicating a reduction in the numbers of myelinated fibers. The mean numbers of myelin lamellae, from an average of all myelinated axons, were not different in control and test population. However, regression analysis of axon sizes by numbers of myelin lamellae revealed significant differences from the normal in 21-day-old undernourished rats. For callosal axons of any size, there were too few myelin lamellae in the undernourished rats. A partial recovery was observed in relatively small fibers by 35 days of age, but no recovery was observed in larger sized fibers. Comparison of the frequency distribution of axon circumferences of myelinated fibers revealed an increase in average axonal caliber. Computation shows that although mean numbers of lamellae were not altered by undernourishment, the axons themselves are increased in size by about 10%. This unexpected result indicates that the relationship normally governing the numbers of myelin lamellae is altered by postnatal nutritional deprivation, and that the relatively larger axon calibers do not produce in the ensheathing oligodendroglia any compensatory increase in the layers of myelin.

Animals↗

A study of forelimb movements evoked by intracortical microstimulation after hemicerebellectomy in newborn, young and adult rats.

Microstimulation of the cerebral motor cortex in normal adult rats evokes low-threshold contralateral and high-threshold ipsilateral forelimb movements. The present study examined the effects of hemicerebellar ablation at different postnatal ages on the current threshold values needed to evoke forelimb movements by intracortical stimulation. Animals that received hemicerebellar lesions at various ages were electrophysiologically tested 4-6 months postoperatively. In all groups, including non-lesion control animals, forelimb movements contralateral to the stimulating electrode were evoked at threshold values of 7-11 microA. Ipsilateral forelimb movements for control animals as well as those receiving cerebellar lesions at 45 or 120 days of age showed significantly higher mean threshold current values, ranging from 38 to 45 microA. In contrast, the mean threshold current values for ipsilateral forelimb movements in adult animals sustaining hemicerebellar lesions at 2, 10 or 21 days of age were significantly lowered, ranging from 16 to 22 microA. Secondary lesions of spared cerebellar tissue or callosal fibers in adult animals that had sustained hemicerebellectomy at two days of age had no effect on the current intensities needed to evoke forelimb responses. In comparison, lesions of the cerebral cortex contralateral to the stimulated cortex increased the threshold for ipsilateral movements and medullary pyramidal lesions ipsilateral to the stimulated cortex both reduced the number of responses and increased the threshold current intensities needed to evoke them. These data indicate that hemicerebellectomy within 3 weeks of age can induce electrophysiological alterations in the responses mediated by the corticospinal tract. These results support previous suggestions of the cerebral cortical involvement in compensation for neonatal cerebellar lesions.

Animals↗

Mechanisms for binocular depth sensitivity along the vertical meridian of the visual field.

By removing the visual cortex unilaterally, and recording along the intact 17/18 border, we have investigated the influence of the corpus callosum on the tuning curves for stimulus disparity of cat cortical neurons. Responses to binocular stimulation were examined to movement in the same (in-phase) and in the opposite direction (antiphase) across the two retinae. In lesioned cats, as in normal cats, units were encountered which showed high sensitivity and narrow tuning for stimulus disparity. In contrast to normal cats, however, lesioned cats showed a reduced proportion of units displaying moderate binocular interactions, as well as a substantial increase in disparity-insensitive cells. The loss of disparity sensitivity after decortication was associated with a reduced incidence of both selectivity for the direction of stimulus motion and binocular activation. No large differences between the preparations were seen, however, in the ocular dominance of the total populations of cells. Differences between the normal and lesioned cats were found in binocular responses to in-phase but not to antiphase stimulation motion. Tuning curves in lesioned cats showed reduced binocular inhibition but no changes in binocular facilitation. Our findings indicate that callosal input contributes to unit disparity sensitivity by enhancing direction-selective binocular inhibition. The corpus callosum generates disparity sensitivity in a population of units in the superficial cortical layers which may play a particular role in the perception of stereoscopic depth.

Animals↗

Long-lasting potentiation of synaptic transmission requires postsynaptic modifications in the neocortex.

The mechanisms of associative long-lasting potentiation (LLP) of excitatory postsynaptic potentials (EPSPs) were studied in the motor cortex of anesthetized cats. Mono- and oligosynaptic EPSPs were evoked by stimulations of thalamic VL nucleus, pyramidal tract, callosal and somatosensory system and paired with orthodromic, antidromic or current-induced action potentials. EPSP-spike stimulus pairs with 0.1-0.2 Hz frequency and 0-200 ms interstimulus intervals induced increases in the amplitudes and durations of EPSPs for 40-60 min or longer after 20-50 pairings. The LLP was prevented when postsynaptic firing was blocked by intracellular current injection or by juxtasomatic application of gamma-aminobutyric acid. LLP was also prevented when the level of intracellular free calcium was lowered by the intracellular injection of the calcium chelator EGTA or when neuronal transport was blocked by the intracellular injection of colchicine. Neither EGTA nor colchicine blocked postsynaptic firing. Thus, these findings show that LLP in the neocortex is a postsynaptic phenomenon which requires conjunctive pre- and postsynaptic activity, adequate levels of intracellular free calcium, and functional intracellular transport.

Action Potentials↗

Structural and metabolic alterations in rat cerebral cortex induced by prenatal exposure to ethanol.

The effects of prenatal exposure to ethanol on glucose utilization in specific laminae of mature rat cerebral cortex were examined. Pregnant hooded rats were fed a liquid diet containing 35% ethanol-derived calories (E) or pair-fed an isocaloric liquid control diet (C) on gestational days 7-21. The cytoarchitecture of motor areas 4 and 6/8 and of somatosensory areas 3 and 2 of 105 day old, male pups was examined in Cresyl violet-stained sections. The glucose utilization of these cortical regions was assessed using a 2-deoxyglucose autoradiographic technique. Overall, cortex was significantly thinner (5-10%) in E-treated rats than in C-treated rats, but with few exceptions, the thickness of individual laminae was not significantly affected by prenatal treatment. Despite these small structural differences, the overall glucose utilization in areas 4, rostral 6/8 3, and 2 of E-treated rats was significantly less (21-24%) than in C-treated rats. Layer IV was the most affected by the prenatal ethanol exposure (29%) and layers I and VI were the least affected (14-22%). The metabolism of caudal area 6/8 was not significantly affected by gestational exposure to ethanol. These results indicate that thalamic and callosal connections and corticospinal projection neurons are specifically affected by prenatal exposure to ethanol. Such alterations may underlie the learning deficits and motor dysfunction characteristic of fetal alcohol syndrome.

Animals↗

Immunocytochemical evidence for glutamatergic cortico-cortical connections in monkeys.

Retrograde transport of horseradish peroxidase and immunocytochemical visualization of glutamate (Glu) were combined to investigate the neurotransmitter used by cortico-cortical neurons in the first (SI) and second (SII) somatic sensory areas of macaque monkeys. The majority of association and callosal neurons in SI and SII were immunoreactive for an antiGlu serum: evidence was therefore obtained in support of a role for Glu, or a closely related compound, as the synaptic transmitter used by cortico-cortical fibers.

Animals↗

Somatosensory receptive fields of fibres in the rostral corpus callosum of the cat.

The corpus callosum is the principal neocortical commissure which transmits lateralized information between the hemispheres. The aim of the present experiment was to study the receptive field (RF) properties of somatosensory callosal fibres in the cat. The callosum was approached under direct visual control and axonic responses were recorded under N2O anaesthesia using tungsten microelectrodes or, mostly, glass micropipettes. RFs representing all the sensory submodalities tested (light touch, medium and deep pressure, joint movement and light pinches) were found to be present in the axons which travelled through the callosum. Rapidly adapting units were more common than slowly adapting ones. The axial and para-axial portions of the body accounted for about three-fifths of all RFs, followed by the head (about one-fifth), with the rest responding to stimulation of the extremities. The medial borders of most of the unilateral RFs situated on the trunk and, to a lesser degree, the head, extended to the mid-line. The results are interpreted in terms of the roles of the corpus callosum in mid-line fusion and interhemispheric transfer.

Afferent Pathways↗

Topography of the corpus callosum in the cat.

Discrete application of horseradish peroxidase to the corpus callosum in cats produced labeled neurons within a dorsoventrally elongated cortical territory. The rostrocaudal position of the territory corresponded with that of the applications. Callosal fibers from the ventral half of the frontal cortex passed through the rostrum, and those from the ventral occipital and dorsal temporal cortex passed through the ventral splenium. These results indicate a sectorial topographical correspondence between the corpus callosum and the cortex.

Animals↗

Bilateral interaction in the second somatosensory area (SII) of the cat and contribution of the corpus callosum.

There are indications in the literature that convergent ipsilateral and contralateral input to the second somatosensory area (SII) may interact. Single unit activity of SII bilateral cells was studied to evaluate the impact of simultaneous bilateral stimulation of the receptive fields (RF) on neural discharge. The cellular responses to unilateral ipsilateral and contralateral, as well as to bilateral stimulation were compared. 22% of bilateral cells showed interaction, usually facilitation. Bilaterally evoked responses were found to be as great as 250% of the strongest unilateral response. Only bilateral responses stronger or weaker than the dominant unilateral response by at least 50% were considered as interactive. The great majority of interactive cells had their RF on the forelimb and were responsive to deep stimulation. The corpus callosum appears to be responsible for part of the observed interaction since in callosotomized cats only 5% of bilateral cells were interactive. A non-callosal ipsilateral pathway must be postulated because both bilaterality and bilateral interaction persist to some degree after callosotomy. A putative role for bilateral interaction in sensory-motor integration is discussed.

Animals↗

Antibody to a soluble protein purified from brain selectively labels layer V corticofugal projection neurons in rat neocortex.

An antibody to a soluble protein (protein 36) isolated and purified from rat brain labels the cell bodies and processes of pyramidal cells within layer V of the rat neocortex. We have used the fluorescent retrograde axonal tracer, Fast blue, in combination with FITC immunocytochemistry to determine the projection sites of the cortical neurons detected by this antibody. Retrogradely labeled pyramidal tract neurons and corticotectal neurons are labeled with the protein 36 antibody, but the callosally projecting neurons within layer V are not. Thus within the neocortex the antibody to protein 36 may selectively detect a particular class of neuron, the corticofugal projection neurons of layer V.

Animals↗

Neurotensin innervation of the human cerebral cortex: lack of colocalization with catecholamines.

We have localized neurotensin (NT) with immunocytochemical methods in the normal human cerebral cortex. Extensive areas of the frontal cortex, the hippocampal formation, and selected areas of the parietal, temporal and occipital lobes, were examined using post-mortem brain tissue. The peptidergic innervation was characteristically restricted to the limbic belt and to the dorsally contiguous regions. NT-labeled perikarya were found throughout the subiculum, including its dorsal supra-callosal continuation. NT terminal plexuses were particularly abundant in layers I-VI of the anterior cingulate cortex, in layer I of area 32 and of medical areas 9, 8, 6 and in layers II-III of area 29, of the presubiculum and entorhinal cortex. Elsewhere, NT fibers were scarce being more frequent in layer I. This regional and laminar pattern differed significantly from that of tyrosine hydroxylase (TH), which was used to label catecholaminergic axons, and preferentially the dopaminergic ones. Even in zones where TH and NT innervations were abundant, such as the anterior cingulate cortex or area 32, double-labeling procedures disclosed no colocalized fibers. The lack of NT-TH colocalization in human, contrasts with previous findings in the rodent cortex, where a contingent of the DA cortical afferents contains NT. The DA mesocortical neuronal population, labeled by TH antisera, thus seems to change its chemical phenotype, by losing the expression of an associated peptidergic neurotransmitter; this could be related to the predominant extension in the ascent of the phylogenetic scale of the non-colocalized, type of cortical DA innervation which is also found in rodents. The possible origins of the cortical, non-dopaminergic NT innervation in human are discussed: thalamo-cortical, subiculo-cortical or intrinsic. Such cortical NT innervation could be very important in limbic circuitry as a regulatory peptide in affective processes and could be involved in the physiology of pain and memory.

Adult↗

Individual differences in brain asymmetries and fiber composition in the human corpus callosum.

There have been several recent reports concerning individual differences in the gross morphometry of the human corpus callosum. However, no studies exist on individual differences in the fiber composition of the corpus callosum. Here we report for the first time the relation of fiber composition in specific callosal segments (as seen in light microscopy) to anatomical asymmetries in language-gifted cortex, as a function of sex. We found a significant negative correlation between Sylvian fissure asymmetries and the total numbers of fibers in the isthmus of males, and in the anterior splenium of females. In addition, a population of relatively large fibers (between 1 micron and 3 microns in diameter) in the isthmus showed a strong negative correlation with perisylvian asymmetries only in males. These findings suggest a sex-dependent, pathway-specific decrease in interhemispheric connectivity with increasing lateralization.

Adult↗

Post-activation potentiation in the neocortex: I. Acute preparations.

Long-term potentiation is widely studied as a memory model, and has been demonstrated in a number of subcortical sites in both acute and chronic preparations. In the neocortex, however, most of the demonstrations of LTP have been in neocortical slice or acute preparations, and even these have often required a drug-induced attenuation of inhibition before the LTP could be reliably expressed. In this paper we show that LTP can be reliably expressed in adult rats in a number of neocortical sites, both ipsilateral and contralateral to the site of callosal stimulation. We also show that, when recording field potentials, LTP is expressed roughly equally at all cortical depths. In a third experiment, we monitored input/output (I/O), paired-pulse inhibition and short-term potentiation effects over the course of LTP induction. The ipsilateral responses were, as expected, of shorter latency and larger amplitude than contralateral responses. They also showed small spike-like components that correlated with cell discharge. Nevertheless, the contralateral responses tended to show the largest LTP effects. The paired pulse effect was mainly depression, lasting for up to 3000 ms, at both ipsilateral and control sites. The short-term potentiation components were best fit by two summed exponentials with time constants of about 70 s and 12 min. The LTP effect lasted at least two h which was the longest period monitored in these experiments.

Animals↗

Cellular and extracellular components at nodes of Ranvier in rat white matter.

Rat CNS nodes of Ranvier were investigated by electron microscopy and immunohistochemistry. Nodes along thin callosal axons possess tiny node gaps containing few or no astrocytic processes. Nodes along thick spinal axons exhibit spatious node gaps containing relatively few irregularly arranged astrocytic processes. Antibodies against HNK-1, chondroitin sulfate, tenascin or NSP-4 do not label small nodes but stain large nodes. We conclude that rat CNS fibers do not exhibit a strict relation between nodal complexity and fiber size comparable to that found in rat PNS fibers.

Animals↗

Sex differences in the distribution of axon types within the genu of the rat corpus callosum.

Neuroanatomical sex differences have been documented in the rat neocortex, including dimorphism of its predominant commissure, the corpus callosum (CC). In particular, CC sex differences have been reported in the ultrastructure of the posterior callosal region, the splenium. Since the CC is a heterogeneous fiber tract with its axons arising from distinct cortical areas and passing through restricted regions along its length, it became of interest to ascertain whether cellular sexual dimorphisms may also be present in another division of the CC. To test this hypothesis, electron microscopy was used to examine axon composition in adult male and female rats in the anterior portion, the genu. The number and size of axons, the thickness of the myelin sheath, and the area within the genu occupied by these constituents, were quantified. Results showed a significant sex difference in the ratio of unmyelinated to myelinated axons, with females having a larger proportion of unmyelinated fibers. This effect was present for both (1) the number of axons, and (2) the area taken up by axonal fibers. No differences were found in the size of either axon type, or for myelin thickness. Comparison of these results with those from the splenium and possible mechanisms underlying this dimorphism are discussed.

Analysis of Variance↗

Post-activation potentiation in the neocortex. IV. Multiple sessions required for induction of long-term potentiation in the chronic preparation.

The neocortex in chronically prepared rats is very resistant to the induction of long-term potentiation (LTP). In the first of two experiments described in this paper, we tried unsuccessfully to induce neocortical LTP within one session by coactivating basal forebrain cholinergic and cortical inputs to our neocortical recording site. In the second experiment, we tested a new procedure which involved the application of repeated conditioning sessions over several days. This procedure was suggested by our finding that kindling-induced potentiation (KIP) of cortical field potentials could be reliably triggered but was slow to develop. We administered 30 high frequency trains per day to the corpus callosum for 25 days. LTP in callosal-neocortical field potentials became clear after about 5 days of stimulation and reached asymptotic levels by about 15 days. After the termination of treatment, LTP persisted for at least 4 weeks, the duration of our post-stimulation test period. As in previous experiments on kindling-induced potentiation, the potentiation effects were clear in both early population spike components and in a late (probably disynaptic) component. The monosynaptic EPSP component was often depressed, but this may have been due to competing field currents generated by the enhanced population spike activity. We discuss these results in the context of theories emphasizing slower but more permanent memory storage in neocortex compared to the hippocampus.

Animals↗