The Neuroanatomist's Dream, the Problems and Solutions, and the Ultimate Aim

3 pages.-- PMID: 18982097 [PubMed].-- PMCID: PMC2570081.The principal goal in neuroanatomy is to define the detailed structural design of the nervous system. This challenge is one of the first steps towards understanding how neural circuits contribute to the functional organization of the nervous system, both in health and disease. The main difficulties involve unraveling the extraordinary complexity of the nervous system and to define how information flows through this finely organized synaptic network. Over the years, neuroanatomy has evolved considerably thanks to the use of classical techniques and the introduction of new procedures (DeFelipe, 2002), including: axonal transport methods to trace connections; electron microscopy to better understand synaptic connectivity; immunocytochemistry to map protein expression and the distribution of particular types of neurons; in situ hybridization to map gene expression; intracellular labeling of physiologically characterized neurons to visualize their morphology; and other powerful techniques to examine the organization of the nervous system. Among the most appealing new tools are the molecular/genetic approaches to activate, inactivate and label active neurons and synapses (Marek and Davis, 2003; Dymecki and Kim, 2007; Kuhlman and Huang, 2008). In turn, as more detailed circuit diagrams become available, the more we will learn about the role of each element in the circuit through computer simulations, and this will enable the response properties of individual neurons to be correlated with the activity in cortical circuits, an attractive bridge between anatomy, physiology and computation (Segev and London, 2000; Markram, 2006). Additionally, the magnitude of morphological, molecular and physiological data collectively generated is now so colossal that even at the cellular level it is necessary to develop neuronal classification systems, in order to help the scientific community in each field to establish and maintain an effective communication and interchange of information (Ascoli et al., 2008). Thus, we have to learn not only how to manage the growing amount of multidisciplinary data but also, how to communicate this knowledge.Peer reviewe

Goodbye Ted (An Obituary for Edward G. Jones)

Peer Reviewe

Cortical GABAergic Neurons: Stretching It

In the cerebellum and basal ganglia, projection neurons are GABAergic; but in the cerebral cortex, there has been a historically strong dichotomy between glutamatergic projection neurons and GABAergic local circuit neurons. While this dichotomy is overwhelmingly valid, it is now clear that a small population of long-distance projecting GABAergic neurons occurs in primates, as well as in cats and rodents. Beyond their well-documented existence, however, the functional significance, ontogeny, and connectivity of this intriguing subpopulation remain obscure

Cortical White Matter: Beyond the Pale

The tracts within the subcortical white matter and corpus callosum provide an anatomical connectivity that is essential for normal cognitive functioning. These structures are predominantly made up of axons that are myelinated or unmyelinated, and entering or exiting the overlying gray matter. As is increasingly recognized, however, the white matter territory is neither inert nor static. It has its own microenvironment, consisting of scattered neurons, abundant glia, and blood vessels; but at the same time it is an integrated component with the much more neuron dense gray matter

Pericellular Innervation of Neurons Expressing Abnormally Hyperphosphorylated Tau in the Hippocampal Formation of Alzheimer's Disease Patients

Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered

Synaptic connections of calretinin-immunoreactive neurons in the human neocortex

Previous immunocytochemical studies in the cerebral cortex of various species have shown that the calcium-binding protein calretinin (CR) labels specific subpopulations of nonspiny non-pyramidal cells (interneurons). The present study attempts to characterize morphologically and chemically the microcircuitry of CR-immunoreactive (CR-ir) neurons in the human temporal neocortex. Postembedding immunocytochemistry for CR and GABA and combination immunocytochemistry for OR and non-phosphorylated neurofilament protein (NPNFP) or for CR and the calcium-binding proteins parvalbumin (PV) and calbindin (CB) showed CR multiterminal endings frequently innervating the distal apical dendrite or the cell body and proximal dendrites of NPNFP-ir or CB-ir pyramidal cells, respectively. Cell bodies of interneurons immunoreactive for CB or PV were innervated only occasionally by CR multiterminal endings, whereas certain GABA neurons were surrounded by them. Furthermore, CR-ir axon terminals formed either symmetrical (the majority) or asymmetrical synapses with a variety of postsynaptic elements. These results indicate that different subpopulations of CR interneurons exist that are specialized for selective innervation of somatic or dendritic regions of certain pyramidal and nonpyramidal neurons.Peer Reviewe

The Neocortical Column

In the middle of the twentieth century, Rafael Lorente de Nó (1902?1990) introduced the fundamental concept of the ?elementary cortical unit of operation,? proposing that the cerebral cortex is formed of small cylinders containing vertical chains of neurons (Lorente de Nó, 1933, 1938). On the basis of this idea, the hypothesis was later developed of the columnar organization of the cerebral cortex, primarily following the physiological and anatomical studies of Vernon Mountcastle, David Hubel, Torsten Wiesel, János Szentágothai, Ted Jones, and Pasko Rakic (for a review of these early studies, see Mountcastle, 1998). The columnar organization hypothesis is currently the most widely adopted to explain the cortical processing of information, making its study of potential interest to any researcher interested in this tissue, both in a healthy and pathological state. However, it is frequently remarked that the nomenclature surrounding this hypothesis often generates problems, as the term ?Column? is used freely and promiscuously to refer to multiple, distinguishable entities, such as cellular or dendritic minicolumns or afferent macrocolumns, with respective diameters of menor que50 and 200?500 ?m. Another problem is the degree to which classical criteria may need to be modified (shared response properties, shared input, and common output) and if so, how. Moreover, similar problems arise when we consider the need to define area-specific and species-specific variations. Finally, and what is more an ultimate goal than a problem, it is still necessary to achieve a better fundamental understanding of what columns are and how they are used in cortical processes. Accordingly, it is now very important to translate recent technical advances and new findings in the neurosciences into practical applications for neuroscientists, clinicians, and for those interested in comparative anatomy and brain evolution

The pyramidal cell in cognition: A comparative study in human and monkey

Here we present evidence that the pyramidal cell phenotype varies markedly in the cortex of different anthropoid species. Regional and species differences in the size of, number of bifurcations in, and spine density of the basal dendritic arbors cannot be explained by brain size. Instead, pyramidal cell morphology appears to accord with the specialized cortical function these cells perform. Cells in the prefrontal cortex of humans are more branched and more spinous than those in the temporal and occipital lobes. Moreover, cells in the prefrontal cortex of humans are more branched and more spinous than those in the prefrontal cortex of macaque and marmoset monkeys. These results suggest that highly spinous, compartmentalized, pyramidal cells (and the circuits they form) are required to perform complex cortical functions such as comprehension, perception, and planning