Von Economo Neurons in the Elephant Brain

Von Economo neurons (VENs), previously found in humans, all of the great ape species, and four cetacean species, are also present in African and Indian elephants. The VENs in the elephant are primarily found in similar locations to those in the other species. They are most abundant in the frontoinsular cortex (area FI) and are also present at lower density in the anterior cingulate cortex. Additionally, they are found in a dorsolateral prefrontal area and less abundantly in the region of the frontal pole. The VEN morphology appears to have arisen independently in hominids, cetaceans, and elephants, and may reflect a specialization for the rapid transmission of crucial social information in very large brains. Anat Rec 2009. © 2008 Wiley‐Liss, Inc.     

Morphology of spiny neurons in the human entorhinal cortex: intracellular filling with lucifer yellow

The present study was designed to investigate the morphology of spiny neurons in the human entorhinal cortex. Coronal entorhinal slices (n = 67; 200 microm thick) were obtained from autopsies of three subjects. Spiny neurons (n = 132) filled with Lucifer Yellow were analysed in different subfields and layers of the entorhinal cortex. Based on the shape of the somata and primary dendritic trees, spiny neurons were divided into four morphological categories; (i) classical pyramidal, (ii) stellate, (iii) modified stellate, and (iv) horizontal tripolar cells. The morphology of filled neurons varied more in different layers than in the different subfields of the entorhinal cortex. In layer II, the majority (81%) of spiny neurons had stellate or modified stellate morphology, but in the rostromedial subfields (olfactory subfield and rostral subfield) there were also horizontal tripolar neurons. Dendritic branches of layer II neurons extended to layer I (94%) and to layer III (83%). Unlike in layer II, most (74%) of the filled neurons in layers III, V and VI were classical pyramidal cells. The majority of pyramidal cells in the superficial portion of layer III had dendrites that extended up to layer II, occupying the space between the neuronal clusters. Some dendrites reached down to the deep portion of layer III. Apical dendrites of layer V and VI pyramidal cells traveled up to the deep portion of layer III.Our data indicate that the morphology of spiny neurons in different layers of the human entorhinal cortex is variable. Vertical extension of dendritic branches to adjacent layers supports the idea that inputs terminating in a specific lamina influence target cells located in various entorhinal layers. There appears to be more overlap in the dendritic fields between superficial layers II and III than between the superficial (II/III) and deep (V/VI) layers, thus supporting the idea of segregation of information flow targeted to the superficial or deep layers in the human entorhinal cortex.     

Morphological alterations in the occipital cortex of aged rats with impaired memory: A Golgi–Cox study

This study investigated a possible link between morphological alterations of pyramidal neurons in layer V of the occipital cortex and the degree of spatial memory impairment in aged rats. Measurements of cortical thickness, density of dendritic branching, and spine counts were carried out in young adult (5 months old) and aged (26 months old) Long-Evans female rats on Golgi–Cox silver-stained material. Using the water-maze task, well- and poorly performing rats were distinguished statistically on the basis of their reference-memory scores. When subsequently compared with young rats or to aged rats with good performances, the well-performing rats had a reduced cortical thickness and exhibited weaker high-order branching of basal dendrites on their pyramidal neurons. When dendritic spines were counted on a 50-m-long straight portion of a basal dendrite, no difference was observed between young and aged rats. Our results suggest that structural alterations affecting pyramidal neurons in the occipital cortex of aged rats may contribute to spatial memory impairment. Indeed, in a subpopulation of well-performing aged rats, these structural alterations were less marked than in the population of bad performers.     

Age-dependent effect of cholinergic lesion on dendritic morphology in rat frontal cortex

Previously, we demonstrated that plasticity of frontal cortex is altered in aging rats: 3 months after surgery, excitotoxic lesions of the nucleus basalis magnocellularis (NBM) produce larger declines in dendritic morphology in frontal cortex of aged rats relative to young adults. To determine whether the differential effect of the lesion was due specifically to loss of cholinergic input from the NBM, we assessed dendritic morphology in frontal cortex after specific cholinergic depletion in young adult, middle-aged, and aged male rats. Rats received unilateral sham or 192-IgG-saporin lesions of the NBM. Two weeks after surgery, brains were stained using a Golgi-Cox procedure. Dendritic morphology was quantified in pyramidal neurons in layers II-III of frontal cortex. Although lesions altered apical dendrites at all ages, these effects were most pronounced in aged rats. In addition, lesions produced marked atrophy of basilar dendrites in middle-aged and aged rats only. Thus, the differential dendritic atrophy resulting from NBM lesions in aged rats occurs within 2 weeks after lesion, and results specifically from loss of cholinergic innervation.     

Quantitative analysis of the dendritic morphology of corticocortical projection neurons in the macaque monkey association cortex

The polymodal association areas of the primate cerebral cortex are heavily interconnected and play a crucial role in cognition. Area 46 of the prefrontal cortex in non-human primates receives direct inputs from several association areas, among them the cortical regions lining the superior temporal sulcus. We examined whether projection neurons providing such a corticocortical projection differ in their dendritic morphology from pyramidal neurons projecting locally within area 46. Specific sets of corticocortical projection neurons were identified by in vivo retrograde transport in young macaque monkeys. Full dendritic arbors of retrogradely labeled neurons were visualized in brain slices by targeted intracellular injection of Lucifer Yellow, and reconstructed three-dimensionally using computer-assisted morphometry. Total dendritic length, numbers of segments, numbers of spines, and spine density were analyzed in layer III pyramidal neurons forming long projections (from the superior temporal cortex to prefrontal area 46), as well as local projections (within area 46). Sholl analysis was also used to compare the complexity of these two groups of neurons.Our results demonstrate that long corticocortical projection neurons connecting the temporal and prefrontal cortex have longer, more complex dendritic arbors and more spines than pyramidal neurons projecting locally within area 46. The more complex dendritic arborization of such neurons is likely linked to their participation in cortical networks that require extensive convergence of multiple afferents at the cellular level.     

The efferent projections of neurons in the white matter of different cortical areas of the adult rat

Summary Injection of Fast Blue into different cortical areas (frontal, parietal, anterior and posterior cingulate cortex) revealed that neurons in the white matter (interstitial neurons) give rise to association fibers which project mostly to the gray matter of the overlying cytoarchitectonic area, but which may extend also over different cytoarchitectonic areas. The rostrocaudal extent of the projecting axons was up to 1 mm in the frontal and parietal cortex, and up to 3.5 mm in the cingulate cortex. Concurrent processing for dihydronicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry showed that 70% of cortically projecting interstitial neurons were NADPH-d-positive. An analysis of neuronal morphology suggests that the Fast-Blue-labeled, NADPH-d-negative neurons may represent displaced pyramidal neurons of layer VIb; the Fast-Bluelabeled and NADPH-d-positive neurons have bipolar or multipolar dendritic trees, constituting a population of nonpyramidal interstitial neurons that project into the cortical gray matter.     

Environmental enrichment: effects on stereotyped behavior and dendritic morphology

We evaluated whether environmental enrichment-related effects on the development of stereotyped behavior in deer mice were associated with alterations in dendritic morphology. Deer mice were reared under enriched or standard housing conditions and then tested in automated photocell detectors and classified as stereotypic or nonstereotypic. Dendritic morphology was assessed in layer V pyramidal neurons of the motor cortex, medium spiny neurons of the dorsolateral striatum, and granule cells of the dentate gyrus using Golgi-Cox histochemistry. Enriched nonstereotypic mice exhibited significantly higher dendritic spine densities in the motor cortex and the striatum than enriched stereotypic or standard-cage mice. Significant increases in dendritic arborization following environmental enrichment also were observed. These results suggest that the enrichment-related prevention of stereotyped behavior is associated with increased dendritic spine density.     

Dendritic morphology of callosal and ipsilateral projection neurons in monkey prefrontal cortex

Subpopulations of cortical pyramidal neurons have been distinguished based on the projection target of their principal axons or by their dendritic morphology. In this study, we sought to test the hypothesis that pyramidal neurons in monkey prefrontal cortex that furnish callosal or ipsilateral projections have distinctive dendritic morphologies. Retrogradely-labeled, Fast Blue-containing callosal and ipsilateral neurons were intracellularly filled with Lucifer Yellow, immunoconverted, and reconstructed. Quantitative measurements of the size and complexity of the dendritic arbor, including total dendritic length, horizontal extent, number of branch points, maximum branch order, and number of segments, as well as spine density, were made. In general, callosal neurons had larger and more complex dendritic arbors for both apical and basilar dendritic trees than did ipsilateral neurons. The greatest difference was in total dendritic length; the apical and basilar trees of callosal neurons were 34 and 25% longer, respectively. In addition, spine density was also significantly greater on the apical and basilar dendrites of callosal neurons. These findings could not be explained by differences in somal size or completeness of dendritic filling between callosal and ipsilateral neurons.Our observations support the hypothesis that callosal and ipsilateral neurons differ on a number of measures of dendritic size and complexity. Furthermore, these findings imply that these two subpopulations of pyramidal cells differ in the number and perhaps types of excitatory inputs that they receive. Finally, differences in the dendritic morphology of callosal and ipsilateral neurons have implications for understanding the functional attributes of these two populations of cells, as well as for the characterization of pyramidal neurons in human disease states.     

The morphology and laminar distribution of cortico-pulvinar neurons in the Rhesus monkey

Summary Using autoradiography and the horseradish peroxidase method, the morphology and laminar distribution of cortico-pulvinar neurons and the reciprocity of connections between pulvinar and cortex were examined in five Rhesus monkeys which had received medial, lateral and inferior pulvinar nucleus injections of both tritiated amino acids and horseradish peroxidase.Cortico-pulvinar neurons were identified in one heterotypical cortical area (area 17) and in many homotypical areas in frontal (areas 45, 46, 11, 12), parietal (5, 7), occipital (18, 19) and temporal (20, 21, 22) lobes. The cortico-pulvinar neurons were pyramidal in shape and ranged in size from small to large. In heterotypical cortex they were found in layers V and VI whereas in area 17 they were found only in layer Vb. Reciprocal connections between pulvinar and cortex were a feature of homotypical but not heterotypical cortex.     

Zinc-rich afferents to the rat neocortex: projections to the visual cortex traced with intracerebral selenite injections

Infusion of sodium selenite to the occipital cortex of the rat was used for the specific tracing of zinc-rich pathways. Large numbers of labeled somata were found ipsilaterally in the visual, orbital and frontal cortices, and contralaterally in homotopic and heterotopic visual areas. Labeled neurons were also found ipsilaterally in the retrosplenial, parietal, sensory-motor, temporal and perirhinal cortex. In contrast to the cortico-cortical connections, ascending afferents to the visual cortex were not zinc-rich except for a few labeled neurons in the claustrum. Additional injections showed reciprocal zinc-rich connections between the visual cortex and the orbital and frontal cortices. The latter cortices also received ascending zinc-rich afferents from the claustrum. Selenite injections revealed the layered distribution and the morphology of these labeled neurons in the neocortex. Zinc-rich neurons were found in layers II–III, V and VI. However, none was found in layer IV. Zinc-rich somata appeared as pyramidal and inverted neurons. The contrasting chemical properties of cortical and subcortical visual afferents may account for the functional differences between these systems.     

Alterations of dendritic protrusions over the first postnatal year of a mouse: an analysis in layer VI of the barrel cortex

Dendritic spines are small protrusions that serve as the principal recipients of excitatory inputs onto cortical pyramidal cells. Alterations in spine and filopodia density and morphology correlate with both developmental maturity and changes in synaptic strength. In order to better understand the developmental profile of dendritic protrusion (dendritic spines + filopodia) morphology and density over the animal’s first postnatal year, we used the Golgi staining technique to label neurons and their dendritic protrusions in mice. We focused on quantifying the density per length of dendrite and categorizing the morphology of dendritic protrusions of layer VI pyramidal neurons residing in barrel cortex using the computer assisted reconstruction program Neurolucida. We classified dendritic protrusion densities at seven developmental time points: postnatal day (PND) 15, 30, 60, 90, 180, 270, and 360. Our findings suggest that the dendritic protrusions in layer VI barrel cortex pyramidal neurons are not static, and their density as well as relative morphological distribution change over time. We observed a significant increase in mushroom spines and a decrease in filopodia as the animals matured. Further analyses show that as the animal mature there was a reduction in pyramidal cell dendritic lengths overall, as well as a decrease in overall protrusion densities. The ratio of apical to basilar density decreased as well. Characterizing the profile of cortical layer VI dendritic protrusions within the first postnatal year will enable us to better understand the relationship between the overall developmental maturation profile and dendritic spine functioning.     

Effect of acetyl-L-carnitine treatment on some behavioural, histochemical and histological parameters of methylazoxymethanol microencephalic rats

The effect of methylazoxymethanol (MAM) administration at the 15th gestational day on some behavioural and morpho-functional parameters of rat brain was investigated. The effect of a 13-15-day treatment of acetyl-L-carnitine on the same parameters was also assessed. MAM microencephalic rats showed a significant impairment in water-maze and pole-climbing tests. The histochemical reactivity of the enzyme NADH2-tetrazolium reductase (NADHR) at the level of frontal and occipital cortex, neostriatum and hippocampus was remarkably reduced. Also cholinacetyltransferase (ChAT) immunoreactivity within nerve cell bodies of the pontine tegmentum was decreased in MAM-treated animals. On the contrary, acetylcholinesterase (AChE) reactivity was increased in all the investigated brain areas with the sole exception of the neostriatum. Nissl reactivity was decreased in the cytoplasm of the pyramidal neurons of the frontal cortex and hippocampus, and slightly increased in the cytoplasm of pyramidal neurons of the occipital cortex of MAM microencephalic rats. Acetyl-L-carnitine treatment improved the behaviour of microencephalic rats in water-maze and pole-climbing tests. Moreover the substance stimulated NADHR reactivity in the cerebral cortex and hippocampus as well as ChAT immunoreactivity in the cytoplasm of neurons of the raphe pontine nuclei. Pharmacological treatment reduced AChE reactivity in the cerebral cortex and the hippocampus, and improved the pattern of Nissl reactivity within all brain areas examined.     

Evidence for a neurotropic role of noradrenaline neurons in the postnatal development of rat cerebral cortex

Summary The effects of neonatal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA; 1–4 doses of 100 mg/kg body weight s.c.) on the postnatal development of pyramidal neurons in several cortical regions of the rat was studied using a Golgi-Cox neuronal impregnation technique. Rats were sacrificed in the adult stage (eight weeks) and the following regions were studied: anterior frontal cortex, posterior frontal cortex (including motor cortex), anterior parietal cortex (including sensory cortex), posterior parieto-occipital cortex and cingulate cortex. Significant alterations were seen in animals which received four doses of 6-OHDA. These alterations can be summarized as follows: (1) a decreased length and branching of basolateral dendrites of pyramidal cells, with loss of dendritic spines, which were found in both the internal pyrimidal layer (layer V) and the external pyramidal layer (layer III), most abundantly in the frontal cortex and cingulate cortex; (2) an increased number of pyramidal cells of layer V with premature apical dendritic termination in layer III rather than the usual termination in layers I and II. This was most abundant in the cingulate cortex; (3) occasional disorientation of pyramidal cell apical dendrites away from the normal vertical plane by 15 or more degrees, seen in frontal, parietal and cingulate cortex; (4) an increased number of pyramidal cells with rounded somatic contours, found in frontal, anterior parietal and cingulate cortex. These phenomena were occasionally seen in normal cortex, but were significantly increased in their occurrence after four doses of 6-OHDA. Such alterations were not significant in rats treated with one or three doses of 6-OHDA. The extent and severity of morphological alterations correlate with reductions in endogenous noradrenaline (NA) in cerebral cortex, which was found to average 50% of control levels after one dose of 6-OHDA, an 80% reduction after three doses, and a 97–98% reduction after four doses, suggesting that the NA denervation must be almost complete to result in readily detectable significant morphological changes in the development of cortical pyramidal cells. No consistent changes in endogenous dopamine (DA) levels were observed, except for an increase in the cingulate cortex. The anatomical alterations in pyramidal cells described in the present study suggest that NA neurons which project into the cerebral cortex have a neurotrophic role in the postnatal development of cortex.     

Morphological and electrophysiological characteristics of pyramidal tract neurons in the rat

Summary Responses evoked in neurons of rat sensorimotor cortex upon stimulation of the pyramidal tract and ipsilateral cerebral peduncle were analysed using intracellular recording. Neurons responding antidromically to pyramidal tract stimulation (PT cells) and neurons failing to respond anti-dromically but exhibiting orthodromic responses were both stained by intracellular injection of horse-radish peroxidase (HRP). Layer V pyramidal neurons, including those responding antidromically, exhibited prominent long lasting membrane hyperpolarizations and inhibitions of action potentials following pyramidal tract or cerebral peduncle stimulation. Upon passage of polarizing intracellular current two components were identified within the hyperpolarizing potential. A short duration initial component readily reversed with hyperpolarizing current. Frequently this earlier component over-lapped a period of early excitation consisting of action potentials arising from recurrent EPSPs or large slow depolarizing potentials (SDPs). The second, much longer duration hyperpolarizing component did not reverse with passage of hyperpolarizing current and was often followed by a rebound period of depolarization and action potential generation. Both the excitatory and the inhibitory portions of these responses could be demonstrated in animals with acute thalamic transections severing the ascending lemniscal pathway to cortex. Following intracellular staining with HRP, two types of PT cells were identified by their different intracortical axonal arborizations. Most of the injected neurons had local axonal fields extending widely in layers V and VI, but with few or no collaterals extending radially toward the more superficial layers. A second type of PT cell had axon collaterals limited to a narrow zone around the dendritic field but extending radially as far as layer I. Cells of both types were observed to send axon collaterals into neostriatum. Both types of neurons exhibited morphological and physiological characteristics of slow PT cells, and we could find no cells comparable to the fast conducting PT cells observed in other species.Supported by NIH grants NS 20743 (to CJW), NS 20702 (to STK) and a FRSQ fellowship (to PL)     

Elephants Have Relatively the Largest Cerebellum Size of Mammals

The current study used MR imaging to determine the volume of the cerebellum and its component parts in the brain of three adult male African elephants (Loxodonta africana) and compared this with published data from Asian elephants and other mammalian species including odontocete cetaceans, primates, chiropterans, insectivores, carnivores, and artiodactyls. The cerebellum of the adult elephant has a volume of ～925 mL (average of both African and Asian species). Allometric analysis indicates that the elephant has the largest relative cerebellum size of all mammals studied to date. In addition, both odontocete cetaceans and microchiropterans appear to have large relative cerebellar sizes. The vermal and hemispheric components of the African elephant cerebellum are both large relative to other mammals of similar brain size, however, for odontocete cetaceans the vermal component is small and the hemispheric component is large. These volumetric observations are related to life‐histories and anatomies of the species investigated. The current study provides context for one aspect of the elephant brain in the broader picture of mammalian brain evolution. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Postweaning social isolation enhances morphological changes in the neonatal ventral hippocampal lesion rat model of psychosis

Neonatal ventral hippocampal (nVH) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Recently, we reported that nVH-lesions result in significant decreases in both length of dendrites and dendritic density of spines of pyramidal neurons of the prefrontal cortex (PFC) and in the density of dendritic spines of medium spiny neurons of the nucleus accumbens (NAcc). Moreover, postweaning social isolation induces major decreases in dendritic spiny density of PFC neurons. We investigated here the comparative dendritic morphology of PFC pyramidal neurons and NAcc medium spiny neurons in nVH rats, following social isolation after weaning (8 weeks). Morphological characteristics of dendrites were measured using the Golgi-Cox procedure followed by a Sholl analysis. Social isolation (SI) by itself induced decreases in dendritic length and dendritic spine density of the NAcc. In socially isolated nVH-lesion rats decrease in dendritic length in PFC and NAcc neurons were exacerbated whereas an increase in spine density of medium spiny neurons was observed in the NAcc. These results indicate that nVH-lesions alter dendritic morphology of NAcc and PFC neurons. These anatomical modifications in both structures may be relevant to behaviors observed in schizophrenia.     

Aging and cholinergic deafferentation alter GluR1 expression in rat frontal cortex

Previously, we demonstrated that plasticity of frontal cortex is altered in aging rats: lesions of the nucleus basalis magnocellularis (NBM) produce larger declines in dendritic morphology in frontal cortex of aged rats compared to young adults. Cholinergic afferents from the NBM modulate glutamatergic transmission in neocortex, and glutamate is known to be involved in dendritic plasticity. To begin to identify possible mechanisms underlying age-related differences in plasticity after NBM lesion, we assessed the effect of cholinergic deafferentation on expression of the AMPA receptor subunit GluR1 in frontal cortex of young adult and aging rats. Young adult, middle-aged, and aged rats received sham or 192 IgG-saporin lesions of the NBM, and an unbiased stereological technique was used to estimate the total number of intensely GluR1-immunopositive neurons in layer II-III of frontal cortex. While the number of GluR1-positive neurons was increased in both middle-aged and aged rats, lesions markedly increased the number of intensely GluR1-immunopositive neurons in frontal cortex of young adult rats only. This age-related difference in lesion-induced expression of AMPA receptor subunit protein could underlie the age-related differences in dendritic plasticity after NBM lesions.     

Manipulation of gonadal hormones in neonatal rats alters the morphological response of cortical neurons to brain injury in adulthood

The authors examined the effects of sex and neonatal hormones on the response of pyramidal cells (Layer III, parietal cortex) to injury of the medial frontal cortex in the adult rat. At birth, males were gonadectomized (GDX) or sham-operated. Females were given testosterone (T) or oil injections. In adulthood, rats that had been left intact at birth were GDX, and they then received bilateral medial frontal cortex lesions or sham surgery. Rats not exposed to T at birth exhibited losses of dendritic arbor (males GDX at birth) or dendritic spine density (oil-treated females). Compensation after cortical injury is dependent on the rat's sex and history of exposure to gonadal steroids.     

Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor

We have previously shown that the serotonergic input on Cajal-Retzius cells, mediated by 5-HT(3) receptors, plays an important role in the early postnatal maturation of the apical dendritic trees of layer 2/3 pyramidal neurons. We reported that knockout mice lacking the 5-HT(3A) receptor showed exuberant apical dendrites of these cortical pyramidal neurons. Because model studies have shown the role of dendritic morphology on neuronal firing pattern, we used the 5-HT(3A) knockout mouse to explore the impact of dendritic hypercomplexity on the electrophysiological properties of this specific class of neurons. Our experimental results show that hypercomplexity of the apical dendritic tuft of layer 2/3 pyramidal neurons affects neuronal excitability by reducing the amount of spike frequency adaptation. This difference in firing pattern, related to a higher dendritic complexity, was accompanied by an altered development of the afterhyperpolarization slope with successive action potentials. Our abstract and realistic neuronal models, which allowed manipulation of the dendritic complexity, showed similar effects on neuronal excitability and confirmed the impact of apical dendritic complexity. Alterations of dendritic complexity, as observed in several pathological conditions such as neurodegenerative diseases or neurodevelopmental disorders, may thus not only affect the input to layer 2/3 pyramidal neurons but also shape their firing pattern and consequently alter the information processing in the cortex.