Ultrastructure of Dendritic Spines: Correlation Between Synaptic and Spine Morphologies

Dendritic spines are critical elements of cortical circuits, since they establish most excitatory synapses. Recent studies have reported correlations between morphological and functional parameters of spines. Specifically, the spine head volume is correlated with the area of the postsynaptic density (PSD), the number of postsynaptic receptors and the ready-releasable pool of transmitter, whereas the length of the spine neck is proportional to the degree of biochemical and electrical isolation of the spine from its parent dendrite. Therefore, the morphology of a spine could determine its synaptic strength and learning rules

A coming-of-age story: adult neurogenesis or adolescent neurogenesis in rodents?

It is surprising that after more than a century using rodents for scientific research, there are no clear, consensual, or consistent definitions for when a mouse or a rat becomes adult. Specifically, in the field of adult hippocampal neurogenesis, where this concept is central, there is a trend to consider that puberty marks the start of adulthood and is not uncommon to find 30-day-old mice being described as adults. However, as others discussed earlier, this implies an important bias in the perceived importance of this trait because functional studies are normally done at very young ages, when neurogenesis is at its peak, disregarding middle aged and old animals that exhibit very little generation of new neurons. In this feature article we elaborate on those issues and argue that research on the postnatal development of mice and rats in the last 3 decades allows to establish an adolescence period that marks the transition to adulthood, as occurs in other mammals. Adolescence in both rat and mice ends around postnatal day 60 and therefore this age can be considered the onset of adulthood in both species. Nonetheless, to account for inter-individual, inter-strain differences in maturation and for possible delays due to environmental and social conditions, 3 months of age might be a safer option to consider mice and rats bona fide adults, as suggested by The Jackson Labs

Neuroanatomical and psychological considerations in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is associated with a variety of structural and psychological alterations. Recently, there has been renewed interest in using brain tissue resected during epilepsy surgery, in particular `non-epileptic¿ brain samples with normal histology that can be found alongside epileptic tissue in the same epileptic patients ¿ with the aim being to study the normal human brain organization using a variety of methods. An important limitation is that different medical characteristics of the patients may modify the brain tissue. Thus, to better determine how `normal¿ the resected tissue is, it is fundamental to know certain clinical, anatomical and psychological characteristics of the patients. Unfortunately, this information is frequently not fully available for the patient from which the resected tissue has been obtained ¿ or is not fully appreciated by the neuroscientists analyzing the brain samples, who are not necessarily experts in epilepsy. In order to present the full picture of TLE in a way that would be accessible to multiple communities (e.g., basic researchers in neuroscience, neurologists, neurosurgeons and psychologists), we have reviewed 34 TLE patients, who were selected due to the availability of detailed clinical, anatomical, and psychological information for each of the patients. Our aim was to convey the full complexity of the disorder, its putative anatomical substrates, and the wide range of individual variability, with a view toward: (1) emphasizing the importance of considering critical patient information when using brain samples for basic research and (2) gaining a better understanding of normal and abnormal brain functioning. In agreement with a large number of previous reports, this study (1) reinforces the notion of substantial individual variability among epileptic patients, and (2) highlights the common but overlooked psychopathological alterations that occur even in patients who become ¿seizure-free¿ after surgery. The first point is based on pre- and post-surgical comparisons of patients with hippocampal sclerosis and patients with normal-looking hippocampus in neuropsychological evaluations. The second emerges from our extensive battery of personality and projective tests, in a two-way comparison of these two types of patients with regard to pre- and post-surgical performance.This work was supported by grants from the following entities: Grant PID2021-127924NB-I00 funded by MCIN/AEI/10.13039/501100011033; Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066); and CSIC Interdisciplinary Thematic Platform (PTI) Cajal Blue Brain (PTI-BLUEBRAIN; Spain). RA was supported by ANDIA grant #0011-3947-2021-000023 from the Gobierno de Navarra

Training future generations to deliver evidence-based conservation and ecosystem management

1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Catecholaminergic innervation of pyramidal neurons in the human temporal cortex

In the human neocortex, catecholaminergic connections modulate the excitatory inputs of pyramidal neurons and are involved in higher cognitive functions. Catecholaminergic fibers form a dense network in which it is difficult to distinguish whether or not target specificity exists. In order to shed some light on this issue, we set out to quantify the catecholaminergic innervation of pyramidal cells in different layers of the human temporal cortex (II, IIIa, IIIb, V and VI). For this purpose, pyramidal cells were labeled in human cortical tissue by injecting them with Lucifer Yellow, and then performed immunocytochemistry for the rate limiting catecholamine synthesizing enzyme tyrosine hydroxylase (TH) to visualize catecholaminergic fibers in the same sections. Injected cells were reconstructed in three dimensions and appositions were quantified (n = 1503) in serial confocal microscopy images of each injected cell (n = 71). We found TH-immunoreactive appositions (TH-ir) in all the pyramidal cells analyzed, in both the apical and basal dendritic regions. In general, the density of TH-ir apposition was greater in layers II, V and VI than in layers IIIa and IIIb. Furthermore, TH-ir appositions showed a regular distribution in almost all dendritic compartments of the apical and basal dendritic arbors across all layers. Hence, it appears that all pyramidal neurons in the human neocortex receive catecholaminergic afferents in a rather regular pattern, independent of the layer in which they are located. Since pyramidal cells located in different layers are involved in different intrinsic and extrinsic circuits, these results suggest that catecholaminergic afferents may modify the function of a larger variety of circuits than previously thought. Thus, this aspect of human cortical organization is likely to have important implications in cortical function. © The Author 2005. Published by Oxford University Press. All rights reserved.Peer Reviewe

The neuropathology of temporal lobe epilepsy: primary and secondary changes in the cortical circuits and epileptogenicity

Presentado en el I Congreso de la Liga Española contra la Epilepsia, celebrado en Bilbao del 14 al 17 de noviembre de 2001. Simposio I: Avances en la Fisiopatología de la Epileptogénesis Moderadores: J.L. Herranz, P. MadozTemporal lobe epilepsy is associated to many disorders localized to the neocortex, the hippocampal formation or both (dual pathology). The most common pathologies are mesial sclerosis, tumours, malformations and scars. However, these alterations are not intrinsically epileptogenic, as they are also seen in patients who do not develop epilepsy. Thus, the cortical tissue in the damaged brain undergoes changes that may become a primary epileptogenic region. This region, in turn, may induce the formation of secondary epileptogenic regions situated at some distance from the primary focus. Development. In this paper we consider the possibility that in both the primary and secondary epileptogenic regions there are similar changes in the neuronal circuits which induce epileptic activity. In the case of the primary epileptogenic regions, these changes occur non-specifically following an initial lesion or precipitating factor (e.g. a tumour) which induces gliosis and neuronal loss around the lesion. These changes give rise to a perilesional synaptic reorganization (elimination of connections with or without the formation of new synapses) which causes the onset and continuation of epileptic activity. However, the changes in the circuits in the secondary epileptogenic regions are the result of epileptic activity originated in the primary epileptogenic region which is propagated by specific anatomical connections. This anomalous activity causes changes in the target region (gliosis and neuronal loss) which leads to epileptogenic synaptic reorganization similar to that occurring in the primary perilesional areas.Este trabajo ha sido financiado por la DGICYT (PM990105), por la Comunidad Autónoma de Madrid (0.8.5/0036/2000) y por una beca predoctoral del Ministerio de Ciencia y Tecnología, FP 2000-4939 (L.A.).Peer reviewe

Microstructure of the neocortex: Comparative aspects

18 pages, 5 figures, 5 tables.-- PMID: 12815249 [PubMed].The appearance of the neocortex, its expansion, and its differentiation in mammals, represents one of the principal episodes in the evolution of the vertebrate brain. One of the fundamental questions in neuroscience is what is special about the neocortex of humans and how does it differ from that of other species? It is clear that distinct cortical areas show important differences within both the same and different species, and this has led to some researchers emphasizing the similarities whereas others focus on the differences. In general, despite of the large number of different elements that contribute to neocortical circuits, it is thought that neocortical neurons are organized into multiple, small repeating microcircuits, based around pyramidal cells and their input-output connections. These inputs originate from extrinsic afferent systems, excitatory glutamatergic spiny cells (which include other pyramidal cells and spiny stellate cells), and inhibitory GABAergic interneurons. The problem is that the neuronal elements that make up the basic microcircuit are differentiated into subtypes, some of which are lacking or highly modified in different cortical areas or species. Furthermore, the number of neurons contained in a discrete vertical cylinder of cortical tissue varies across species. Additionally, it has been shown that the neuropil in different cortical areas of the human, rat and mouse has a characteristic layer specific synaptology. These variations most likely reflect functional differences in the specific cortical circuits. The laminar specific similarities between cortical areas and between species, with respect to the percentage, length and density of excitatory and inhibitory synapses, and to the number of synapses per neuron, might be considered as the basic cortical building bricks. In turn, the differences probably indicate the evolutionary adaptation of excitatory and inhibitory circuits to particular functions.This work was supported by grants from the Spanish Ministry of Science and Technology (DGCYT PM99-0105) and the Comunidad de Madrid (08.5/0027/2001.1). L A-N is supported by fellowship from the Spanish Ministry of Science and Technology (FP2000-4989).Peer reviewe

Quantitative analysis of parvalbumin-immunoreactive cells in the human epileptic hippocampus

13 pages, 6 figures, 3 tables.-- PMID: 17850980 [PubMed].-- Printed version published Oct 12, 2007.Hippocampal sclerosis is the most frequent pathology encountered in mesial temporal structures resected from patients with intractable temporal lobe epilepsy and it mainly involves hippocampal neuronal loss and gliosis. These alterations are accompanied by changes in the expression of a variety of molecules in the surviving neurons, as well as axonal reorganization in both excitatory and inhibitory circuits. The alteration of a subpopulation of GABAergic interneurons that expresses the calcium binding protein parvalbumin (PV) is thought to be a key factor in the epileptogenic process. We investigated the distribution and density of parvalbumin-immunoreactive (PV-ir) neurons in surgically resected hippocampal tissue from epileptic patients with and without sclerosis. Using quantitative stereological methods, we show for the first time that there is no correlation between total neuronal loss and PV-ir neuronal loss in any of the hippocampal fields. We also observed higher values of the total neuronal density in the sclerotic subiculum, which is accompanied by a lower density of PV-ir when compared with non-sclerotic epileptic and autopsy hippocampi. These findings suggest that, the apparently normal subiculum from sclerotic patients also shows unexpected changes in the density and proportion of PV-ir neurons.This work was supported by the following institutions: Spanish Ministry of Education and Science (BFI2003-02745, BFI2003-01018, BFU2006-13395); Comunidad de Madrid (grant 08.5/0027/2001.1); and research fellowships for A.A. (Ricerca Fondazione Mariani, Grant R-04-40) and L.A.-N. (BFI2003-02745).Peer reviewe