Evolution and function of calcium-binding proteins.
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The superior colliculus is a midbrain structure serving visual, multisensory and sensorimotor processing. Throughout various collicular layers, visual afferents are linked together with afferents related to other sensory modalities as well as with afferents from sources not easily subsumed under the term 'sensory'. These inputs are orchestrated in a topographic fashion and led to premotor neurons that are important elements in generating saccadic eye movements and orientation movements of other kinds. Using immunocytochemical techniques to chart the distribution of various substances serving neurotransmission and neuromodulation, it was found that many of them, e.g. acetylcholinesterase (AChE), choline acetyltransferase, the enkephalins, substance P, and parvalbumin, relate to repetitive structural islands, or modules, in the superior colliculus. From studies on the distribution of three further neuroactive substances in rat superior collicular tissue: the calcium binding protein calretinin, the growth and plasticity related protein neuromodulin (GAP-43), and a glutamate receptor of the NMDA-type, we were led to conclude (1) that the intermediate layers of the superior colliculus are composed not of two, but of at least three disjunct types of modules, (2) that not just the intermediate layers but more or less the whole superior colliculus is an assemblage of modules, and (3) that, besides topographic connectivity and laminar structuring, the modules constituting an iterative partitioning represent a third major feature of superior collicular architecture. The origin of the collicular mosaic is considered under an evolutionary perspective, and a hypothesis is presented stating that the pattern of AChE-rich modules on the level of the multimodal collicular layers can be predicted from retinal ganglion cell topography.
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A comparative analysis of the area of the cortex that is adjacent to the primary visual area (V1), indicates that the lateral extrastriate cortex of primitive mammals was likely to contain only a single visuotopically organized field, the second visual area (V2). Few, if any, other visual areas existed. The opposing hypothesis, that primitive mammals had a 'string' of small visual areas in the cortex lateral to V1 (as in some rodents), is not supported by studies of the organization of extrastriate cortex in other mammals, nor by the variability in this organization among extant rodents. A critical re-analysis of published evidence on the presence of multiple areas adjacent to V1 in some rodents has led to alternative interpretations of the organization of the areas in these regions.
The second symposium on 'The Developmental Basis of Evolutionary Change' was held at the University of Chicago, IL, USA, from 25 to 28 October 2001.
Several approaches to the spectrum of obsessive-compulsive spectrum disorders have been put forward, each based on a rather different framework. To some extent, overlaps exist among these approaches, indicating that the neurobiology of OCD and related disorders is increasingly consolidated; however, important differences exist between these approaches, and many questions are unanswered, demonstrating that more work is necessary to fully delineate OCD and its subtypes and their relationships to other putative obsessive compulsive spectrum disorders. Despite the need for substantial additional research on the neurobiology of the obsessive-compulsive spectrum, this construct already has heuristic value in the clinical and research setting. It reminds clinicians to ask OCD patients about comorbid spectrum disorders, and it suggests the possible value of anti-OCD agents and behavioral techniques in patients for whom treatments were previously unavailable. It reminds investigators to consider possibly overlapping and differentiating mechanisms in several disorders. Ultimately, the delineation of such mechanisms will allow for a more rigorous approach to the putative obsessive-compulsive spectrum disorders.
Both living cell and central nervous system can be treated as objects similar to artificial neural networks, actively studied now. One can see deep analogies between evolutionary processes in these systems, and correspondences can be established between some phenomena and objects. These are: genome vs. memory, gene vs. symbol, cell type vs. image, mitosis vs. sleep, organism vs. perception state, species vs. language, fertilization vs. attention, meiosis vs. paradoxal sleep. There is reason to study these correspondences on more technical level being based upon network nature of the living cell and nervous system.
This is an overview of our studies on insulin and insulin-like growth factor-I (IGF-I) interactions with their own and each other's receptors in the lamprey (Lampetra fluviatilis L.), an extant representative of the ancient vertebrate group of Agnathans as compared to mammal (rat). Lamprey insulin receptor shows species specificity, namely, it binds its own insulin with higher affinity than mammalian hormone. Nevertheless, and unlike mammalian insulin receptor, lamprey receptor discriminates relatively poorly between insulin and IGF-I. Autophosphorylation patterns are identical for both receptors. In contrast, IGF-I receptors in lamprey tissues are very similar to mammalian IGF-I receptors confirming known evolutionary conservatism of IGF receptor system. Presumed common evolutionary origin of insulin and IGF-I receptors and poor ability of lamprey insulin receptor to discriminate between two ligands, implies that lamprey insulin receptor is closer to putative ancestral protein that IGF-I receptor. Contrary to the common belief, ambient temperatures for lampreys (4-15 degrees C) put no constraints on either downregulation of receptors or the endocytosis of hormone-receptor complexes.
The evolution of brain injury was examined in mice subjected to focal cerebral ischemia as induced by 30 min of intraluminar thread occlusion of the middle cerebral artery, followed by 3 h to 3 days of reperfusion. Metabolic dysfunctions were studied by 3H-leucine autoradiography for the measurement of cerebral protein synthesis and by regional ATP bioluminescent imaging. Metabolic changes were compared with responses of the genes c-fos, c-jun, heat-shock protein gene (hsp)72, p53-activated gene (pag)608 and caspase-3, which were investigated by in situ hybridization histochemistry and immunocytochemistry, and correlated with the degree of DNA fragmentation, as assessed by the terminal TdT-mediated dUTP-biotin nick end labeling method. Intraluminar thread occlusion led to a reproducible reduction of cerebral laser Doppler flow to 20-30% of control. Thread withdrawal was followed by a short-lasting post-ischemic hyperperfusion to approximately 120%. In non-ischemic control animals, fractional protein synthesis values of 0.81+/-0.26 and 0.94+/-0.23 were obtained. Thread occlusion resulted in a suppression of protein synthesis throughout the territory of the middle cerebral artery after 3 h of reperfusion (0.04+/-0.08 in caudate-putamen and 0.14+/-0.19 in somatosensory cortex, P<0.05). Protein synthesis partly recovered in the cortex after 24 h and 3 days (0.71+/-0.40 and 0.63+/-0.26, respectively), but remained suppressed in the caudate-putamen (0.14+/-0.22 and 0.28+/-0.28). Regional ATP levels did not show any major disturbances at the reperfusion times examined. Thread occlusion resulted in a transient increase of c-fos mRNA levels in ischemic and non-ischemic parts of the cortex and caudate-putamen at 3 h after ischemia, which suggests that spreading depressions were elicited in the tissue. At the same time, c-jun and hsp72 mRNAs were elevated only in ischemic brain areas showing inhibition of protein synthesis. C-fos and c-jun responses completely disappeared within 24 h of reperfusion. Hsp72 mRNA levels remained elevated in the cortex after 24 h, but decreased to basal values in the caudate-putamen. Twenty-four hours after reperfusion, pag608 and caspase-3 mRNA levels increased in the caudate-putamen, where protein synthesis rates were still reduced, and remained elevated even after 3 days. However, pag608 and caspase-3 mRNA levels did not increase in the cortex, where protein synthesis recovered. After 24 h and 3 days, functionally active p20 fragment of caspase-3 was detected in the caudate-putamen, closely associated with the appearance of DNA fragmented cells. Neither activated caspase-3 nor DNA fragmentation were noticed in the cortex.In summary, the suppression of protein synthesis is reversible in the ischemia-resistant cortex following 30 min of thread occlusion in mice, but persists in the vulnerable caudate-putamen. In the caudate-putamen, apoptotic programs are induced, closely in parallel with the manifestation of delayed cell death. Thus, the recovery of protein synthesis may be a major factor influencing tissue survival after transient focal ischemia.