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PubMed1982

Efferent connections of dorsal and ventral agranular insular cortex in the hamster, Mesocricetus auratus.

The anterior portion of rodent agranular insular cortex consists of a ventral periallocortical region (AIv) and a dorsal proisocortical region (AId). Each of these two cortical areas has distinct efferent connections, but in certain brain areas their projection fields are partially or wholly overlapping. Bilateral projections to layers I, III and VI of medial frontal cortex originate in the dorsal agranular insular cortex and terminate in the prelimbic, anterior cingulate and medial precentral areas; those originating in ventral agranular insular cortex terminate in the medial orbital, infralimbic and prelimbic areas. The dorsal and ventral regions of the agranular insular cortex project topographically to the ipsilateral cortex bordering the rhinal fissure, which includes the posterior primary olfactory, posterior agranular insular, perirhinal and lateral entorhinal areas. Fibers to these lateral cortical areas were found to travel in a cell-free zone, between cortical layer VI and the claustrum, which corresponds to the extreme capsule. The dorsal and ventral regions send commissural projections to layer I, lamina dissecans and outer layer V, and layer VI of the contralateral homotopical cortex, via the corpus callosum. Projections from the ventral and dorsal regions of the agranular insular cortex to the caudatoputamen are topographically arranged and terminate in finger-like patches. The ventral, but not the dorsal region, projects to the ventral striatum and ventral pallidum. The thalamic projections of the ventral and dorsal regions are largely overlapping, with projections from both to the ipsilateral reticular nucleus and bilaterally to the rhomboid, mediodorsal, gelatinosus and ventromedial nuclei. The heaviest projection is that to the full anteroposterior extent of the medial segment of the mediodorsal nucleus. Brainstem areas receiving projections from the ventral and dorsal regions include the lateral hypothalamus, substantia nigra pars compacta, ventral tegmental area and dorsal raphe nucleus. In addition, the ventral region projects to the periaqueductal gray and the dorsal region projects to the parabrachial and ventral pontine nuclei. These efferent connections largely reciprocate the afferent connections of the ventral and dorsal agranular insular cortex, and provide further support for the concept that these regions are portions of an outer ring of limbic cortex which plays a critical role in the expression of motivated, species-typical behaviors.

Amygdala↗

PubMed1985

Frontal cortex projections to the amygdaloid central nucleus in the rabbit.

Evidence has recently been presented which demonstrates that the amygdaloid central nucleus projects directly upon cardiovascular/autonomic regulatory nuclei of the dorsal medulla and that in the rabbit this nucleus may influence cardiovascular activity during emotional states. The present study is one of a series of investigations designed to provide information on the innervation of the central nucleus in the rabbit and describes the topography and origin of frontal cortex projections to the nucleus based upon retrograde and anterograde axonal transport techniques. Injections of horseradish peroxidase or the fluorescent dyes, Bisbenzimide or Nuclear Yellow, into the central nucleus resulted in abundant numbers of retrogradely labeled neurons in three regions of the frontal cortex: the insular cortex on the lateral surface and areas 25 and 32 on the medial surface of the hemisphere. The majority of labeled neurons in the insular cortex were located in layer V of the dorsal and posterior agranular insular regions, although labeled neurons were observed in layer V of the granular insular cortex as well as in layers II and III of the posterior agranular insular cortex. Labeled neurons in areas 25 and 32 were located throughout all layers and the total number of these neurons was substantially less than that observed in the insular cortex. Autoradiographic experiments in which amino acids were injected into the insular cortex resulted in a dense pattern of transported label within the central nucleus that extended rostrally into the sublenticular substantia innominata and lateral component of the bed nucleus of the stria terminalis. Label was also observed in the cortical, lateral, basolateral and basomedial amygdaloid nuclei. In contrast to the projections from the insular cortex, amino acid injections into areas 25 and 32 resulted in only relatively light labeling within the most rostral region of the central nucleus; otherwise the nucleus was partially encapsulated and virtually devoid of label. These results suggest that the insular cortex possesses the potential to directly influence the central nucleus projection to cardiovascular/autonomic regulatory nuclei of the dorsal medulla and thus, together with the amygdaloid central nucleus, appears to be an important component of a forebrain system involved in cardiovascular/autonomic regulation.

Amygdala↗

PubMed1991

The organization of serotonergic projections to cerebral cortex in primates: retrograde transport studies.

Retrograde axonal transport and immunocytochemical methods were utilized to determine the origin of serotonergic afferents to selected primary projection and association areas of cerebral cortex in macaque monkeys. After injections of Fast Blue or Diamidino Yellow in primary motor, somatosensory, or visual cortex, retrogradely labeled neurons are found in both the dorsal and median raphe nuclei. The sets of dorsal raphe neurons which innervate these cortical areas differ in their spatial distributions along the rostrocaudal axis of the brainstem; a coarse rostrocaudal topographic relationship is found between these groups of dorsal raphe neurons and their cortical targets. In contrast, neurons in the median raphe which innervate these primary projection areas are not differentially distributed along the rostrocaudal axis. However, in both the median and dorsal raphe nuclei, most neurons projecting to primary visual cortex are situated lateral to the cells which project to motor and somatosensory areas; many of these visually projecting neurons lie among the fascicles of the medial longitudinal fasciculus. For comparison with the serotonergic innervation of primary projection areas, the locations of raphe cells projecting to three areas of association cortex were examined: dorsolateral prefrontal cortex, area 5 and area 7b. Neurons projecting to each of these association areas are found throughout the dorsal and median raphe nuclei. Their distributions are similar to one another; however, more cells projecting to dorsolateral prefrontal cortex are in the rostral part of the dorsal raphe. The dorsal and median raphe neurons projecting to these association areas are intermingled with neurons projecting to motor and somatosensory cortex, but are medial to most of those projecting to visual cortex. Thus, separate cortical areas are innervated by different sets of raphe neurons; these sets partially overlap, yet differ in their rostrocaudal and mediolateral distributions. Ascending serotonergic projections to cerebral cortex form a widely distributed system which exhibits a highly intricate anatomic organization. The present observations support the hypothesis that the dorsal raphe nucleus is comprised of distinct sets of neurons whose output is distributed to multiple, interconnected cortical areas; these serotonergic projections may play a role in the coordination of excitability in functionally related areas of cortex. In contrast, the serotonergic projections arising from the median raphe appear to be more divergent and are likely to have a global influence on cortical activity. Since these individual raphe nuclei have different projection patterns, they are likely to have distinct functional roles.

Afferent Pathways↗

PubMed1991

Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat.

The organization of connections between the amygdala, prefrontal cortex and striatum was studied using anterograde and retrograde tract tracing techniques in the rat. The anterograde transport of Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin conjugated to horseradish peroxidase was used to examine the striatal projections of the prefrontal cortex. These studies revealed that the prelimbic area of the medial prefrontal cortex projects mainly to the medial part of the striatum, whereas the dorsal agranular insular area of the lateral prefrontal cortex projects mainly to the ventrolateral part of the striatum. The organization of amygdaloid projections to the prefrontal cortex and its associated portions of the striatum was investigated using the fluorescence retrograde tract tracing technique. Different color fluorescent dyes, True Blue and Diamidino Yellow, were injected into the prefrontal cortex and striatum. These studies demonstrated that medial portions of the basolateral nucleus, and adjacent portions of the lateral, basomedial and amygdalo-hippocampal nuclei, project to both the medial prefrontal cortex and its associated medial striatal region. The rostral pole and lateral portions of the basolateral nucleus project to both the lateral prefrontal cortex and its associated lateral striatal region. Many neurons in the basolateral amygdaloid nucleus, and to a lesser extent other amygdaloid nuclei, were double-labeled in these experiments, indicating that these cells send collaterals to both the prefrontal cortex and striatum. These findings indicate that discrete areas of the amygdala, and in some cases individual amygdaloid neurons, can modulate information processing in the first two links of distinct cortico-striato-pallidal systems arising in the medial and lateral prefrontal cortex.

Afferent Pathways↗

PubMed2003

Do rats have a prefrontal cortex?

The lack of a single anatomical or functional definition of 'prefrontal cortex' has led to different and, in some respects, controversial views on the existence of a prefrontal cortex in non-primate mammals, in particular in rats. Until the classic paper by Rose and Woolsey [Res. Publ. Assoc. Nerv. Ment. Dis. 27 (1948) 210], the general idea was that a prefrontal cortex is unique to primate species. Rose and Woolsey's 'prefrontal cortex' definition was based upon a single anatomical criterion, i.e. the cortical projection area of the mediodorsal thalamic nucleus. Single criteria, however, do not appear to be sufficient for defining the prefrontal cortex. Therefore, other anatomical and functional characteristics are currently used to identify the prefrontal cortex in different species. Yet, recently the debate about the nature of the prefrontal cortex in non-primate species has been resumed. In the present paper we will compare the structural and functional characteristics of the prefrontal cortex of nonhuman primates and rats. We will argue that rats have a functionally divided prefrontal cortex that includes not only features of the medial and orbital areas in primates, but also some features of the primate dorsolateral prefrontal cortex.

Animals↗

PubMed2004

Prevention of age-related changes in rat cortex transcription factor activator protein-1 by hypolipidemic drugs.

We sought to investigate if, similar to what has been described in other rodent tissues, ageing changes the activity of several transcription factors, namely signal transducer and activator of transcription, nuclear factor-kappa B (NFkappaB), activated protein-1 (AP-1) and peroxisome proliferator-activated receptor (PPAR), in cortex of Sprague-Dawley rats. We also investigated if the administration of two hypolipidemic drugs, gemfibrozil (GFB) and atorvastatin (ATV), could prevent those changes. To this purpose, we determined the expression and binding activity of these transcription factors in cortex samples from 3-month and 18-month old male and female rats, and in 18-month old rats of both sexes treated for 21 days with a daily dose of 3mg GFB/kg or 10mg ATV/kg. Ageing increased rat cortex NFkappaB binding activity by 35-40%, and decreased by 22-26% the amount of PPARalpha in rats of both sexes, while cortex AP-1 binding activity and c-Jun content were reduced only in old females (-26 and -50%, respectively). Cortex cyclooxigenase-2 (COX-2) and receptor for activated C-kinase 1 (RACK1) expression was also reduced by old age. Hypolipidemic drugs prevented the age-related decrease of cortex AP-1 in old females and increased AP-1 binding activity and c-Jun protein in cortex from both old male and female rats. GFB increased also by 80% the cortex PPARalpha content in old males. Our data indicate that 18-month old rats show signs of cortex biochemical deterioration related to the ageing process, and that hypolipidemic drug administration partially prevents the appearance of some of the age-related changes in cortex biochemistry.

Aging↗

PubMed2004

Acute changes in cortical excitability in the cortex contralateral to focal intracerebral hemorrhage in the swine.

Injury to the cerebral cortex results in functional deficits not only within the vicinity of the lesion but also in remote brain regions sharing neuronal connections with the injured site. To understand the electrophysiological basis of this phenomenon, we evaluated the effects of a focal intracerebral hemorrhage (ICH) on cortical excitability in a remote, functionally connected brain region. Cortical excitability was assessed by measuring the somatic evoked potential (SEP) elicited by electrical stimulation of the swine snout, which is somatotopically represented in the rostrum area of the primary somatosensory (SI) cortex. The SEP was measured on the SI cortex ipsilateral to the site of ICH and on the contralateral SI cortex during the acute period (< or =11 h) after collagenase-induced ICH. The ICH rapidly attenuated the SEP on the ipsilateral cortex as we reported earlier. Interestingly, the ICH also attenuated the SEP on the contralateral SI cortex. Evoked potentials in the contralateral SI cortex showed a gradual decrease in amplitude during this acute period of ICH. We then investigated whether the interhemispheric connections shared by the contralateral SI and the lesion cortex were responsible for the diminished evoked potentials in the uninjured hemisphere after ICH. A separate group of animals underwent corpus callosal transection prior to electrocorticography (ECoG) recordings and ICH injury. Within hours of hemorrhagic injury, a gradual but marked increase in evoked potential amplitude was observed in the homotopic SI cortex of callosotomized animals as compared to pre-injection recordings. The enhancement suggests that there are additional effects of ICH on remote areas functionally connected to the site of injury. Functional deficits were present in both SI cortices within the first several hours of a unilateral injury indicating that the cessation of brain activity in the lesioned SI is mirrored in the contralateral hemisphere. This electrophysiological depression in the uninjured SI cortex is mediated in part by the interhemispheric connections of the corpus callosum.

Animals↗

PubMed2005

Differential distribution of NADPH-diaphorase histochemistry in human cerebral cortex.

Beta-nicotinamidedinucleotide phosphate diaphorase (NADPH-d) colocalizes with NOS in the central nervous system. Two types of NADPH-d-positive neurons are present in the primate cerebral cortex: type 1, intensely and Golgi-like labeled neurons, a subset of GABAergic interneurons; type 2, lightly labeled neurons (divided into two subclasses, a first one having a lightly stained cell body bearing only one short process, and a second one showing intense NADPH-d staining with short processes extending radially). We have analyzed the distribution of NADPH-d activity in human frontal, temporal, and occipital cortical areas, finding remarkable laminar and interareal differences in cell size and distribution of the different cell types. There was a clear bias for type 1 neurons in infragranular layers in all areas considered; both in supra- and infragranular layers, their density was highest in frontal, and lowest in temporal cortex. The density of type 2 neurons was lower supragranularly in temporal cortex and infragranularly in occipital cortex. The overall density of type 2 cells was remarkably higher in occipital cortex than in the temporal and frontal ones. Type 1 neurons were significantly larger than type 2, and were smaller in the supragranular than in the infragranular subzone in occipital and temporal cortex. Type 1 cells were significantly larger in frontal cortex than in occipital and temporal cortex, and type 2 cells were significantly smaller in occipital than in temporal and frontal cortex. These area-related differences might reflect differences between heterotypic and homotypic cortex in the regulation of cortical blood flow.

Axons↗

PubMed2004

Mirtazapine-induced corelease of dopamine and noradrenaline from noradrenergic neurons in the medial prefrontal and occipital cortex.

The novel antidepressant mirtazapine has been shown to increase extracellular noradrenaline and dopamine in the medial prefrontal cortex. Our previous studies indicate that extracellular dopamine in the cerebral cortex originates largely from noradrenergic terminals, such release being controlled by alpha(2)-adrenoceptors. Because mirtazapine inhibits alpha(2)-adrenoceptors, the possibility that it might corelease dopamine and noradrenaline was investigated. By means of microdialysis, the effect of mirtazapine on extracellular dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and noradrenaline in the medial prefrontal cortex, densely innervated by dopaminergic and noradrenergic neurons, and in the occipital cortex, receiving equal noradrenergic but scarce dopaminergic projections, was compared. Basal extracellular concentration of noradrenaline was similar in both cortices, while dopamine in the occipital cortex was only about 50% lower than in the medial prefrontal cortex, reflecting noradrenergic rather than dopaminergic projections. The intraperitoneal (i.p.) administration of mirtazapine (5 and 10 mg/kg) increased extracellular dopamine, DOPAC and noradrenaline to approximately the same extent in both cortices, an effect totally suppressed by the alpha(2)-adrenoceptors agonist clonidine (0.15 mg/kg, i.p.). To exclude the possibility that mirtazapine-induced increase in dopamine might result from reduced dopamine removal from extracellular space, noradrenaline and dopamine uptake mechanisms were blocked by perfusing 100 microM desipramine into either cortex. The combined i.p. administration of mirtazapine (5 mg/kg) and the local perfusion of desipramine produced an additional increase in extracellular dopamine, DOPAC and noradrenaline in the medial prefrontal cortex and occipital cortex compared with the increase produced by either drug given alone. The results suggest that mirtazapine by inhibiting alpha(2)-adrenoceptors produces a corelease of noradrenaline and dopamine from noradrenergic terminals in the cerebral cortex.

Adrenergic Uptake Inhibitors↗

PubMed2005

Intrinsic connections of the cingulate cortex in the rat suggest the existence of multiple functionally segregated networks.

The cingulate cortex is a functionally and morphologically heterogeneous cortical area comprising a number of interconnected subregions. To date, the exact anatomy of intracingulate connections has not been studied in detail. In the present study we aimed to determine the topographical and laminar characteristics of intrinsic cingulate connections in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine. For assessment of these data we further refined and compared the existing cytoarchitectonic descriptions of the two major cingulate constituents, the anterior cingulate and retrosplenial cortices. The results of this study demonstrate that rostral areas, i.e. the infralimbic and prelimbic cortices and the rostral one third of the dorsal anterior cingulate cortex are primarily interconnected with each other and not with other cingulate areas. The caudal two thirds of the dorsal anterior cingulate cortex project to the caudal part of the ventral anterior cingulate cortex, whereas the entire ventral anterior cingulate cortex projects to only the mid-rostro-caudal part of the dorsal anterior cingulate cortex. Dense reciprocal connections exist between the remaining, i.e. the supracallosal parts of the anterior cingulate and retrosplenial cortices with a general rostro-caudal topography, in the sense that the rostral part of the anterior cingulate cortex and caudal part of the retrosplenial cortex are interconnected and the same holds true for the caudal part of the anterior cingulate cortex and rostral part of the retrosplenial cortex. This topographical pattern of intracingulate connections relates to the results of several functional studies, suggesting that specific cingulate functions depend on a number of interconnected cingulate subregions. Through their intricate associational connections, these subregions form functionally segregated networks.

Animals↗

PubMed2005

Effects of single and continuous administration of amyloid beta-peptide (25-35) on adenylyl cyclase activity and the somatostatinergic system in the rat frontal and parietal cortex.

It is unknown whether the amyloid beta-peptide (Abeta), a principal component found in extracellular neuritic plaques in the brain of patients with Alzheimer's disease (AD), is capable of altering adenylyl cyclase (AC) activity and the somatostatin (SRIF) receptor-effector system in the cerebral cortex of the patients. Therefore, the objective of this study was to investigate the effect of the beta fragment, beta (25-35), on AC activity and the somatostatinergic system in the rat frontoparietal cortex. A single dose of beta (25-35) (10microg) injected intracerebroventricularly significantly decreased the density of SRIF receptors (27.4%) and increased their affinity (32.2%) in the frontoparietal cortex. The inhibitory effect of SRIF on basal and forskolin (FK)-stimulated AC activity was significantly lower in the beta (25-35)-treated rats when compared with controls. beta (25-35) did not modify Gialpha1, Gialpha2 nor Gialpha3 levels in membranes from the frontoparietal cortex. Continuous infusion of the peptide induced a decrease in the SRIF receptor density in this brain area to a similar extent as that observed 14 days after the single administration of the peptide. Likewise, this treatment decreased the SRIF receptor density in the frontal cortex (15.3%) and parietal cortex (27.2%). This effect was accompanied by a decrease in the SRIF-mediated inhibition of FK-stimulated AC activity (from 41.6% to 25.6%) in the frontal cortex as well by a decrease in basal AC activity (from 36.9% to 31.6%) and FK-stimulated AC activity (from 35.6% to 27.1%) in the parietal cortex. Continuous infusion of Abeta (25-35) had no effect on Gialpha1, Gialpha2 or Gialpha3 levels in membranes from frontal and parietal cortex. However, this treatment caused a decrease in SRIF-like immunoreactivity content in the parietal (38.9%) and frontal (20.4%) cortex. These results suggest that Abeta might be involved in the alterations of somatostatinergic system reported in AD.

Adenylyl Cyclases↗

PubMed1999

Quantitative analyses of neurons projecting to primary motor cortex zones controlling limb movements in the rat.

The objective was to determine if projections of single neurons to primary motor cortex preferentially terminate in several efferent zones that could form synergies for the execution of limb movements. Intracortical microstimulation was used to identify zones evoking hip flexion (HF), elbow flexion (EF), and both plantarflexion (PF) and dorsiflexion (DF) about the ankle. Histological examination showed that the zones from which some movements were evoked extended beyond the agranular cortex into granular cortex. Fluorogold, Fast blue, and propridium iodide or rhodamine-labeled dextran were injected into three of these four efferent zones in each rat. There was a virtual absence of multiple-labeled cells despite having an intermingling of different-colored cells of which 15% in frontal cortex were less than 1.2 mm away from a neighboring neuron that projected to a different efferent zone. This suggests that single neurons projecting to the motor cortex do not hard-wire specific synergies but rather project to single efferent zones in order to offer the greatest degree of freedom for the generation of movements. The distribution of ventral posterolateral and ventrolateral thalamic nucleus labeling depended on whether the injections were in granular or agranular cortex. Conversely, frontal cortex projections to motor efferent zones were made irrespective of their location in either granular or agranular cortex and thereby supporting their presumed role in the control of movements. Hindlimb motor cortex injections yielded retrograde labeling that extended into the more localised distribution of frontal cortex neurons retrogradely labeled from forelimb injections. This may allow hindlimb movements to be synchronized by forelimb movements during walking on challenging terrain.

Animals↗

PubMed1996

Roles of the lateral suprasylvian cortex in convergence eye movement in cats.

Ocular convergence and lens accomodation were evoked by microstimulation in the lateral suprasylvian area (LS cortex) in the parieto-occipital cortex in the cat. Electrolytic lesions in LS cortex reduced the amplitude and velocity of ocular convergence. Neurons in LS cortex discharged in relation to ocular convergence and/or lens accommodation. These results support the hypothesis that the LS cortex plays an important role in controlling ocular convergence The LS cortex receives visual inputs from cortical visual areas 17, 18 and 19, and in addition from the superior colliculus through the LP nucleus of the thalamus. Electrophysiological recordings have revealed that these visual inputs, which include cues about 3-dimensional target motion, are integrated in the LS cortex. The integrated output from LS cortex may provide the brainstem motor centers with the neural signals that facilitate eye movements, especially when the target is moving at high speeds. Outputs from the LS cortex travel directly to brainstem structures including the superior colliculus and pretectum. Evidence from monkey suggests that information may also travel to the mesencephalic reticular formation, where neurons have been recorded that are related to ocular convergence, lens accomodation or both. Although comparable data is lacking in the cat, it is suggested that the efferent circuit from the LS cortex to the motor nuclei in the brainstem included both the superior colliculus and the mesencephalic reticular formation. It is also suggested that this pathway is rather short, given that the mean latency of the early component of evoked disjunctive eye movements was approximately 60 ms.

Animals↗

PubMed1999

Laminar distribution of pick bodies, pick cells and Alzheimer disease pathology in the frontal and temporal cortex in Pick's disease.

Lesions in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have distinct laminar distributions in the cortex. The objective of the present study was to test the hypothesis that the lesions characteristic of Pick's disease (PD) and AD have distinctly different laminar distributions in cases of PD. Hence, the laminar distribution of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) was studied in the frontal and temporal cortex in nine patients with PD. In 57% of analyses of individual cortical areas, the density of PB was maximal in the upper cortex while in 25% of analyses, the distribution of PB was bimodal with density peaks in the upper and lower cortex. The density of PC was maximal in the lower cortex in 77% of analyses while a bimodal distribution was present in 5% of analyses. The density of NFT was maximal in the upper cortex in 50% of analyses, in the lower cortex in 15% of analyses, with a bimodal distribution in 4% of analyses. The density of SP did not vary significantly with cortical depth in 86% of analyses. The vertical densities of PB and PC were negatively correlated in 12/21 (57%) of brain areas. The maximum density of PB in the upper cortex was positively correlated with the maximum density of PC in the lower cortex. In 17/25 (68%) of brain areas, there was no significant correlation between the vertical densities of PB and NFT. The data suggest that the pathogenesis of PB may be related to that of the PC. In addition, although in many areas PB and NFT occur predominantly in the upper cortex, the two lesions appeared to affect different neuronal populations.

Adult↗

PubMed2003

Morphological changes and stress responses in neurons in cerebral cortex infiltrated by diffuse astrocytoma.

Local dysfunction in cerebral cortex infiltrated by astrocytoma can cause epilepsy and focal neurological deficits, but the cellular pathology of peritumoral cortex remains poorly defined. The aims of the present study were to define the morphological changes which occur in neurons in tumor-infiltrated cerebral cortex, and to determine whether peritumoral neurons show expression of cell stress-related proteins. Archival specimens of diffuse astrocytoma (n = 28) were identified with areas of both tumor-infiltrated cortex and apparently non-infiltrated cortex. Immunohistochemistry was performed to structural neuronal proteins (MAP-2, neurofilament proteins), beta-amyloid precursor protein, growth associated protein-43 and to injury response proteins (poly(ADP-ribose) polymerase, poly(ADP-ribose), c-fos, and c-jun). Tumor-infiltrated cortex revealed neuronal loss and architectural disarray compared to non-infiltrated cortex. Pyramidal neurons showed thinning of the cytoplasmic rim and their neuritic processes showed increasing tortuosity, varicosity, fragmentation and loss, with axonal spheroid formation and dendritic beading. Poly(ADP-ribose) polymerase, poly(ADP-ribose) and c-fos were up-regulated in both infiltrated and non-infiltrated cortex, but c-jun expression was greater in areas of tumor-infiltrated cortex. Surviving neurons in cortex infiltrated by astrocytoma demonstrate, therefore, a sequence of morphological alterations in their dendritic, somatic and axonal compartments, and demonstrate a cell stress response. The patterns of cellular pathology identified suggest possible mechanisms, by which neurons are damaged and eventually lost in peritumoral brain.

Astrocytoma↗

PubMed2004

Assessment of factors regulating axon growth between the cortex and spinal cord in organotypic co-cultures: effects of age and neurotrophic factors.

Axon growth failure in the central nervous system (CNS) of adult animals is thought to be attributable to several factors, including an inadequate intrinsic growth response, the presence of inhibitory molecules, and a lack of adequate neurotrophic support. Here we use a new in vitro assay system to quantitatively assess growth of axons in cortex/spinal cord organotypic co-cultures from neonatal rats. Co-cultures of cortex and spinal cord were prepared from neonatal rats at P3 or P7, and by pairing cortex and spinal cords from different ages. Axon growth from the cortex to the spinal cord was assessed using DiI tract tracing techniques. Axons could be traced from the cortex to the spinal cord in co-cultures in which both tissues were obtained from P3 animals, whereas few axons crossed the cortex/spinal cord boundary in co-cultures from P7 animals. A larger number of axons could be traced across the boundary in co-cultures from P3 animals that were treated with neurotrophins (NGF, BDNF, or NT3), whereas neurotrophins produced minimal growth enhancement in P7 co-cultures. In mixed age co-cultures of P7 cortex with P3 spinal cord, moderate numbers of axons extended between the cortex and spinal cord when cultures were treated with neurotrophins, but few if any crossing axons were detected in co-cultures of P3 cortex with P7 spinal cords. These results indicate that successful growth of axons from the cortex to the spinal cord depends on the developmental age of the tissue terrain (the spinal cord and/or the interface between cortex and spinal cord explants), and to a lesser extent on the developmental state of the cortical neurons, and that axon growth between cortex and spinal cord can be enhanced by exogenous neurotrophins. These co-cultures provide a potentially useful assay for factors that affect axon growth that is intermediate between assays based on dissociated neurons and the intact tissue terrain.

Age Factors↗

PubMed2004

Reappraisal of DL/V4 boundaries based on connectivity patterns of dorsolateral visual cortex in macaques.

We placed injections of 3-5 distinguishable tracers in different dorsolateral locations in the visual cortex of four macaque monkeys to help define the extent of the dorsolateral visual complex (DL) commonly known as area V4. Injections well within DL/V4 region labeled neurons in V2, V3, MT, IT, and sometimes V1. In contrast, injections in caudal area 7a dorsal to current descriptions of DL/V4 produced a different pattern of labeled neurons largely involving posterior parietal and adjoining occipital cortex, as well as cortex of the medial wall. Injections placed in the dorsal prelunate cortex (DP), near the expected location of the dorsal border of DL/V4, labeled neurons in a third pattern, including regions of the posterior parietal and occipital cortex, inferior temporal (IT) cortex, and sometimes parts of dorsal area V2, DL/V4 complex and MT. Injections placed near or ventral to previous estimates of the ventral border of the rostral divisions of DL (DLr) and near the expected rostroventral border of V4 with TEO labeled cells in a pattern distinctively different from either central DL/V4 injections or those dorsal to DL/V4. Injections placed rostroventral to DL/V4 labeled neurons over a large extent of the IT cortex, while failing to label neurons in V1, V2 and MT. Injections that partially involved the rostroventral border of DL/V4 produced a similar pattern of labeled neurons, but also labeled a few cells in ventral V1 and V2, as well as many in DL/V4. Dorsal and rostroventral injections also labeled different regions of the prefrontal cortex, but only DL/V4 injections that included area DP labeled neurons in the prefrontal cortex. The results revealed contrasting and transitional connection patterns for four regions of the dorsolateral visual cortex, and they provided evidence for the locations of dorsal and rostroventral borders of the DL/V4 complex.

Animals↗

PubMed1992

Cerebral cortex ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat.

Hyperammonemia has been suggested to induce enhanced cerebral cortex ammonia uptake, subsequent glutamine synthesis and accumulation, and finally net glutamine release into the blood stream, but this has never been confirmed in liver insufficiency models. Therefore, cerebral cortex ammonia- and glutamine-related metabolism was studied during liver insufficiency-induced hyperammonemia by measuring plasma flow and venous-arterial concentration differences of ammonia and amino acids across the cerebral cortex (enabling estimation of net metabolite exchange), 1 day after portacaval shunting and 2, 4, and 6 h after hepatic artery ligation (or in controls). The intra-organ effects were investigated by measuring cerebral cortex tissue ammonia and amino acids 6 h after liver ischemia induction or in controls. Arterial ammonia and glutamine increased in portacaval-shunted rats versus controls, and further increased during liver ischemia. Cerebral cortex net ammonia uptake, observed in portacaval-shunted rats, increased progressively during liver ischemia, but net glutamine release was only observed after 6 h of liver ischemia. Cerebral cortex tissue glutamine, gamma-aminobutyric acid, most other amino acids, and ammonia levels were increased during liver ischemia. Glutamate was equally decreased in portacaval-shunted and liver-ischemia rats. The observed net cerebral cortex ammonia uptake, cerebral cortex tissue ammonia and glutamine accumulation, and finally glutamine release into the blood suggest that the rat cerebral cortex initially contributes to net ammonia removal from the blood during liver insufficiency-induced hyperammonemia by augmenting tissue glutamine and ammonia pools, and later by net glutamine release into the blood. The changes in cerebral cortex glutamate and gamma-aminobutyric acid could be related to altered ammonia metabolism.

Ammonia↗