Juncal González-Soriano

Morphological types of horizontal cell in rodent retinae: A comparison of rat, mouse, gerbil, and guinea pig

Retinal horizontal cells of four rodent species, rat, mouse, gerbil, and guinea pig were examined to determine whether they conform to the basic pattern of two horizontal cell types found in other mammalian orders. Intracellular injections of Lucifer-Yellow were made to reveal the morphologies of individual cells. Immunocytochemistry with antisera against the calcium-binding proteins calbindin D-28k and parvalbumin was used to assess population densities and mosaics. Lucifer-Yellow injections showed axonless A-type and axon-bearing B-type horizontal cells in guinea pig, but revealed only B-type cells in rat and gerbil retinae. Calbindin immunocytochemistry labeled the A- and B-type populations in guinea pig, but only a homogeneous regular mosaic of cells with B-type features in rat, mouse, and gerbil. All calbindin-immunoreactive horizontal cells in the latter species were also parvalbumin-immunoreactive; comparison with Nissl-stained retinae showed that both antisera label all of the horizontal cells. Taken together, the data from cell injections and the population studies provide strong evidence that rat, mouse, and gerbil retinae have only one type of horizontal cell, the axon-bearing B-type, whereas the guinea pig has both A- and B-type cells. Thus, at least three members of the family Muridae differ from other rodents and deviate from the proposed mammalian scheme of horizontal cell types. The absence of A-type cells is apparently not linked to any peculiarities in the photoreceptor populations, and there is no consistent match between the topographic distributions of the horizontal cells and those of the cone photoreceptors or ganglion cells across the four rodent species. However, the cone to horizontal cell ratio is rather similar in the species with and without A-type cells.

Widespread Changes in Dendritic Spines in a Model of Alzheimer's Disease

The mechanism by which dementia occurs in patients with Alzheimers disease (AD) is not known. We assessed changes in hippocampal dendritic spines of APP/PS1 transgenic mice that accumulate amyloid beta throughout the brain. Three-dimensional analysis of 21,507 dendritic spines in the dentate gyrus, a region crucial for learning and memory, revealed a substantial decrease in the frequency of large spines in plaque-free regions of APP/PS1 mice. Plaque-related dendrites also show striking alterations in spine density and morphology. However, plaques occupy only 3.9% of the molecular layer volume. Because large spines are considered to be the physical traces of long-term memory, widespread decrease in the frequency of large spines likely contributes to the cognitive impairments observed in this AD model.

Gender differences in human cortical synaptic density

Certain cognitive functions differ in men and women, although the anatomical and functional substrates underlying these differences remain unknown. Because neocortical activity is directly related with higher brain function, numerous studies have focused on the cerebral cortex when searching for possible structural correlates of cognitive gender differences. However, there are no studies on possible gender differences at the synaptic level. In the present work we have used stereological and correlative light and electron microscopy to show that men have a significantly higher synaptic density than women in all cortical layers of the temporal neocortex. These differences may represent a microanatomical substrate contributing to the functional gender differences in brain activity.

Morphological alterations to neurons of the amygdala and impaired fear conditioning in a transgenic mouse model of Alzheimer's disease

Patients with Alzheimers disease (AD) suffer from impaired memory and emotional disturbances, the pathogenesis of which is not entirely clear. In APP/PS1 transgenic mice, a model of AD in which amyloid β (Aβ) accumulates in the brain, we have examined neurons in the lateral nucleus of the amygdala (LA), a brain region crucial to establish cued fear conditioning. We found that although there was no neuronal loss in this region and Aβ plaques only occupy less than 1% of its volume, these mice froze for shorter times after auditory fear conditioning when compared to their non‐transgenic littermates. We performed a three‐dimensional analysis of projection neurons and of thousands of dendritic spines in the LA. We found changes in dendritic tree morphology and a substantial decrease in the frequency of large spines in plaque‐free neurons of APP/PS1 mice. We suggest that these morphological changes in the neurons of the LA may contribute to the impaired auditory fear conditioning seen in this AD model. Copyright

Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement

A small peptide from a neuronal cell adhesion molecule enhances synaptic plasticity in the hippocampus and results in improved cognitive performance in rats.

Differential distribution of neurons in the gyral white matter of the human cerebral cortex.

The neurons in the cortical white matter (WM neurons) originate from the first set of postmitotic neurons that migrates from the ventricular zone. In particular, they arise in the subplate that contains the earliest cells generated in the telencephalon, prior to the appearance of neurons in gray matter cortical layers. These cortical WM neurons are very numerous during development, when they are thought to participate in transient synaptic networks, although many of these cells later die, and relatively few cells survive as WM neurons in the adult. We used light and electron microscopy to analyze the distribution and density of WM neurons in various areas of the adult human cerebral cortex. Furthermore, we examined the perisomatic innervation of these neurons and estimated the density of synapses in the white matter. Finally, we examined the distribution and neurochemical nature of interneurons that putatively innervate the somata of WM neurons. From the data obtained, we can draw three main conclusions: first, the density of WM neurons varies depending on the cortical areas; second, calretinin‐immunoreactive neurons represent the major subpopulation of GABAergic WM neurons; and, third, the somata of WM neurons are surrounded by both glutamatergic and GABAergic axon terminals, although only symmetric axosomatic synapses were found. By contrast, both symmetric and asymmetric axodendritic synapses were observed in the neuropil. We discuss the possible functional implications of these findings in terms of cortical circuits. J. Comp. Neurol. 518:4740–4759, 2010.

A Stereological Study of Synapse Number in the Epileptic Human Hippocampus

Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

Calbindin D28k and parvalbumin immunoreactivity in the rabbit superior colliculus: An anatomical study

The expression pattern of two calcium binding proteins (CaBP), calbindin D28k (CB) and parvalbumin (PV), in the superior colliculus (SC) of the adult rabbit, as well as the morphology of the immunoreactive cells were examined. The study was performed on 12 rabbits. Coronal sections from postmortem SC were analyzed by light microscopy, and drawings of CaBP‐labeled cells were obtained using a drawing tube. No previous information is available on either the CB/PV expression or the morphology of CB/PV positive cells in the SC of the adult rabbit. Therefore, in this study we show that CB neurons and neuropil form three main tiers: the first located within the stratum zonale (SZ) and the upper part of the stratum griseum superficiale (SGS), the second located within the stratum griseum intermedium (SGI), and the third, located within the medial and central areas of the stratum griseum profundum (SGP). In contrast to this layer labeling, almost no CB‐positivity is found within the other collicular layers. On the other hand, the densest concentration of PV labeled cells and terminals is found within a single dense tier that spanned the ventral part of the startum griseum superficiale (SGS) and the dorsal part of the stratum opticum (SO). Anti‐PV neurons are also scattered through the deeper layers below the dense tier. In contrast, almost no anti‐PV labeled neurons or neuropil are found within the stratum zonale (SZ) and upper SGS. This distribution represents a new pattern of sublamination in the SC of this species. All the previously described cell types in other mammals are observed in the rabbit SC: marginal cells, horizontal cells, pyriform cells, narrow‐field vertical cells, wide‐field vertical cells, and stellate/multipolar cells. Detailed drawings of all these cellular types are represented to show their complete morphology. The results of this study indicate that both CB and PV are present in a variety of neurons, which present a number of homologies between mammals, but have a different location and/or distribution, according to the different species. These findings are thus relevant to better understand the organisation of the SC in mammals. Anat Rec 259:334–346, 2000.

A Quantitative Study of Ganglion Cells in the Goat Retina

As in a number of mammals, the most prominent feature of the ganglion‐cell layer in the retina of the murciano‐granadina goat is an increase in the density of ganglion cells in the central area, as well as a concentration along a ridge extending horizontally across the retina, below the optic disc, and in the upper temporal retina. Thus, there is an area of maximum density and two streaks that are known as the ‘horizontal’ and ‘vertical’ streak. The isodensity lines of ganglion‐cell distribution is roughly concentric, with their values varying from 304 cells/mm2 in the periphery to 3592 cells/mm2 in the central area, with the cells densely packed. There were some individual differences amongst the animal studied, although all of them were purebred animals.

NADPH-diaphorase distribution in the rabbit superior colliculus and co-localization with calcium-binding proteins

Nitric oxide (NO) and calcium‐binding proteins (CaBP) are important neuromodulators implicated in brain plasticity and brain disease. In addition, the mammalian superior colliculus (SC) has one of the highest concentrations of NO within the brain. The present study was designed to determine the distribution of nitric oxide‐synthesizing neurons in the SC of the rabbit by enzyme histochemistry for reduced nicotinamide adenine dinucleotide phosphate‐diaphorase (NADPH‐d), and its degree of co‐localization with CaBP, parvalbumin (PV) and calbindin (CB). NADPH‐d‐labelled fibres formed dense patches of terminal buttons within the intermediate grey layer and streams of fibres within the deepest layers of SC. Cells expressing NOS constitute a subpopulation of neurons in which practically all cell types are represented. Combined PV/NADPH‐d experiments showed a complete lack of co‐localization within individual neurons and fibres. On the contrary, double‐labelled neurons appeared in CB/NADPH‐d‐stained sections, only in the superficial layers, and mostly in the SGS and SO. These cells, which were intermingled with other neurons containing either NADPH‐d or CB, appear to be a subtype of narrow‐field and wide‐field vertical cells, and display an anterior–posterior gradient of density. Owing to the involvement of the superficial layers of the SC in the organization and integration of the visual information, it is suggested that these neurons may play a concrete role within the visual circuits. Our data indicate a clear selectivity in the expression of NADPH‐d, PV and CB in the SC, and that NO and CB probably serve as co‐modulators and/or co‐transmitters in the connectivity of the superficial layers of this midbrain structure.