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, where as 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.

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.electron microscopy ͉ neocortex ͉ neuronal density ͉ sex

The mechanism by which dementia occurs in patients with Alzheimer's 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.

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.

Patients with Alzheimer's 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 © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

In several mammals only one of the two types of retinal horizontal cell, the axonless A-type, appears to express neurofilaments. Neurofilament immunostaining of rodent retinas reveals a horizontal cell plexus that has previously been interpreted as belonging to A-type cells. Our intracellular Lucifer yellow injections strongly suggest that there are no A-type horizontal cells in rat and gerbil. Counterstaining of dye-injected cellular structures with a neurofilament antibody directly shows that the axon terminal systems of the axon-bearing B-type horizontal cells contain neurofilaments. These unexpected findings explain and reinterpret the neurofilament plexus in rodent retinas. In contrast, Lucifer yellow injections in guinea pig retina reveal both A- and B-type horizontal cells, showing that horizontal cell types are not uniform among rodents. In the guinea pig retina both A-type cells and B-type axon terminal systems contain neurofilaments.

Determining the number of synapses that are present in different brain regions is crucial to understand brain connectivity as a whole. Membrane-associated guanylate kinases (MAGUKs) are a family of scaffolding proteins that are expressed in excitatory glutamatergic synapses. We used genetic labeling of two of these proteins (PSD95 and SAP102), and Spinning Disc confocal Microscopy (SDM), to estimate the number of fluorescent puncta in the CA1 area of the hippocampus. We also used FIB-SeM, a three-dimensional electron microscopy technique, to calculate the actual numbers of synapses in the same area. We then estimated the ratio between the three-dimensional densities obtained with FIB-SEM (synapses/µm 3) and the bi-dimensional densities obtained with SDM (puncta/100 µm 2). Given that it is impractical to use FIB-SEM brain-wide, we used previously available SDM data from other brain regions and we applied this ratio as a conversion factor to estimate the minimum density of synapses in those regions. We found the highest densities of synapses in the isocortex, olfactory areas, hippocampal formation and cortical subplate. Low densities were found in the pallidum, hypothalamus, brainstem and cerebellum. finally, the striatum and thalamus showed a wide range of synapse densities. Determining the number of synapses that are present in different brain regions is crucial to understand brain connectivity as a whole. Synapses can be identified with several methods, including genetic labeling of synaptic scaffolding proteins and electron microscopy (EM). Membrane-associated guanylate kinases (MAGUKs) are a family of scaffolding proteins that participate in the regulation of cell polarity, cell adhesion and synaptic signal transduction 1-3. PSD95 and SAP102 belong to the MAGUK family and are expressed in the postsynaptic density (PSD) of excitatory glutamatergic synapses 4-12 , where they contribute to the recruitment and retention of glutamate receptors 13-15. Genetic labeling of the endogenous PSD95 and SAP102 postsynaptic proteins and imaging using Spinning Disk confocal Microsocpy (SDM) have been proven to be useful for the characterization of synapse diversity in all brain regions of the mouse. SDM is a rapid method that allows the imaging of entire brain sections, so the simultaneous visualization of millions of synapses is made possible, obtaining bi-dimensional densities of fluorescent puncta per surface area (puncta/100 µm 2) 16. Previous attempts have been made to calculate the density of synapses in the brain using EM. This technique allows the identification of individual synapses, although it is restricted to much smaller fields of view. Furthermore, most of these EM studies apply stereological techniques to a limited number of EM sections. Although stereology is a proven valuable method for object counting, the total number of synapses is an estimation which is subject to several technical limitations [see 17 for a review]. In the present study, we use Focused Ion Beam